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Research report Retinal projection to the dorsal raphe nucleus in the Chilean degus (Octodon degus)
Abstract
A substantial projection from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in the Chilean degus, a diurnal / crepuscular hystricomorph rodent. Following intraocular injection of cholera toxin subunit B (CTB), immunocytochemically labeled CTB-positive axons and terminals were observed in all major retinorecipient nuclei as well as in the DRN and periaqueductal gray (PAG) of the mesencephalon. Two streams of optic axons to the DRN were observed: one descending from the optic tract at the level of the pretectum and anterior superior colliculus, the other emerging as a small fascicle at the anterior pole of the inferior colliculus and descending bilaterally through the PAG. Contralateral retinal afferents in the DRN appeared to terminate primarily in the dorsomedial and lateral subdivisions of the DRN, and a less extensive ipsilateral component also was observed. Axonal arborizations were characterized by short branches and multiple varicosities, both in the DRN and in the PAG. The extent and density of DRN retinal afferents were not as extensive as previously observed in Mongolian gerbils using identical techniques, but the retinal-DRN projection is considerably larger in degus than in rats. The functional significance of the retinal-DRN pathway remains to be determined, although a variety of evidence indicates that light may directly affect the activity of neurons and serotonin levels in the DRN. © 2001 Elsevier Science B.V. All rights reserved. Theme: Sensory systems Topic: Subcortical visual pathways
... The present study describes optic afferents that project retrochiasmatic area and subparaventricular zone [7,24], into the dorsal pontine region and terminate in the lateral lateral habenular nucleus [35], anterodorsal thalamus, and component of the parabrachial (PB) nucleus in three lateroposterior nucleus [13,21,28]. Retinal afferents also species: laboratory rats, Mongolian gerbils and Chilean innervate the olfactory tubercle, piriform cortex, and degus, following intraocular injection of an anterograde amygdaloid complex in the basal forebrain tracer, cholera toxin subunit B. These optic axons show [5,6,10,18,26,28,31,35]. ...
... Retinal afferents also species: laboratory rats, Mongolian gerbils and Chilean innervate the olfactory tubercle, piriform cortex, and degus, following intraocular injection of an anterograde amygdaloid complex in the basal forebrain tracer, cholera toxin subunit B. These optic axons show [5,6,10,18,26,28,31,35]. In the mesencephalon, optic affer-morphological characteristics similar to those previously ents also have been observed in the periaqueductal gray described for the retinofugal projection to the dorsal raphe and dorsal raphe nucleus in a variety of species [12-nucleus (DRN) [12,13]. Furthermore, this optic afferent 14,22,36]. ...
... Efrostral pole of the cerebellum. The immunocytochemical ferent targets of the lateral PB include the lateral hypoprocedures used to demonstrate anterograde transport of thalamus, the ventrobasal and visceral relay nuclei of the CTB in optic axons have been described previously thalamus (median preoptic nucleus, ventroposterior par- [1,12,13]. In at least three animals of each species, sections vicellular nucleus) [8,33], which relay nociceptive and containing CTB-labelled axons and terminals were charted visceral information to the limbic forebrain, to the insular from the posterior pole of the superior colliculus to the cortex and to the central nucleus of the amygdala. ...
Following intraocular injection of cholera toxin subunit B (CTB), optic afferents to the dorsal pontine region were observed in Mongolian gerbils, Chilean degus, and laboratory rats. CTB-positive optic axons emerge at the caudal pole of the superior colliculus, descend through the periaqueductal gray, and innervate the lateral parabrachial nucleus. This projection appears to be a continuation of the retinal pathway that innervates the dorsal raphe nucleus in these same species.
... Light promotes sleep in night active animals, so the lack of retinal projections to the VLPO in the diurnal degu was expected. Additionally, other studies show differences in the retinal projections to other areas involved in sleep-wake regulation (Fite & Janusonis, 2001). Both nocturnal and diurnal animals have retinal projections to the SCN along the retino-hypothalamic tract (RHT) (Moore, 1993). ...
... The VLPO, a hypothalamic nuclei key for sleep promotion, has shown a stronger direct retinal projection in the rat, but not the degu. Conversely, the dorsal raphe nuclei (DRN) has demonstrated a stronger retinal input within the diurnal degu, compared to the nocturnal rat (Fite et al., 1999;Fite et al., 2001). Future research should examine the efferents of these key nuclei, which may provide insight into neuroanatomically distinct pathways that serve as the foundation for diurnal/nocturnal differences in sleep. ...
This dissertation examined the impact of sex and development on sleep in the diurnal rodent, Octodon degus. All experiments utilized electrophysiological measures to quantify sleep patterns, brain temperature and locomotor activity (via electroencephalography, thermistor probes, and infrared motion detectors). The descriptive study revealed the diurnal non rapid eye movement sleep (NREMS) patterns of degus and the low levels of rapid eye movement sleep (REMS), with females showing significantly more NREMS amount and consolidation and less REMS compared to males. Sleep intensity (measured by NREMS delta wave activity) was sexually dimorphic, with males demonstrating higher relative levels during the light phase and females exhibiting increases during the dark phase. Circadian gating of sleep was particularly powerful, with both sexes displaying heightened activity around the light-dark transitions. The second set of experiments aimed to elucidate the homeostatic and circadian components of sleep utilizing the 6h sleep deprivation paradigm. Sleep deprivation increased homeostatic drive within both sexes and was mediated by circadian phase. Compensatory mechanisms for sleep recovery differed between sexes, with males demonstrating transient increases in NREMS amount and consolidation while females displayed transitory increases in NREMS consolidation and prolonged elevation of sleep intensity. Lastly, the final experiments aimed to investigate the two components of sleep across development within male degus. While early pubertal degus did not demonstrate a strong preference for diurnal sleep, the rhythmicity of sleep intensity was consistent with previous studies of diurnal mammals. Late pubertal degus demonstrated circadian variation of NREMS and REMS, suggesting there may be a critical window of hormonal influence on sleep within this diurnal rodent. Both age groups displayed significantly increased NREMS parameters in response to a 6h deprivation during the dark phase, yet the circadian component of sleep was dampened during light transition periods, contrasting adult degus patterns. Together, these data highlight Octodon degus as a good diurnal rodent model for investigating the circadian and homeostatic mechanisms of sleep, as well as the interaction of these opponent processes under baseline conditions and following physiological disruption. Furthermore, the slowly developing degu presents a unique opportunity to examine these components in a small diurnal mammal.
... The raphe-SCN tract may be the last link in an indirect neural pathway from the retina, transmitting photic information during early night. A neural pathway linking the retina to the dorsal raphe has been described in the rat [16][17][18], cat [19], gerbil [18;204], Chilean degus [205] and tree shrew [20], but apparently not the hamster [12]. ...
... How does light information reach the SCN via an indirect pathway? A neural pathway linking the retina to the dorsal raphe has been described in the rat [16][17][18], cat [19], gerbil [18;204], Chilean degus [205] and tree shrew [20] (but not the hamster [12]). Whether these incoming neurons synapse with other neurons that project to the SCN is yet to be determined, but provides a plausible means by which light perceived at the retina could reach the SCN. ...
... The large, serotonergic dorsal raphe nucleus (DRN) those of the 'nonimage-forming' subsystem of retinal receives direct retinal afferents in a number of species, afferents, which encodes primarily the photic and temporal including cats [10], rats [9,32], Chilean degus [7], tree characteristics of visual stimulation [2,8,22,23,26]. shrews [31] and Mongolian gerbils [9]. ...
... All provisual systems [3][4][5][6]20,27]. The retinal-DRN pathway cedures were approved by the Institutional Animal Care shows several morphological features [7,9] fluorescent tracers. Using previously determined stereo-Four of nine animals injected showed well-localized taxic coordinates [17], rhodamine-B-isothiocyanate (RITC, tracer injections in both target structures, and no leakage of Sigma) was injected into the DRN using a 10-ml Hamilton either tracer into any other retinorecipient nuclei was syringe, needle and microdrive assembly. ...
Injections of rhodamine-B into the dorsal raphe nucleus (DRN) and Fluoro-Gold into the lateral geniculate nucleus (LGN) revealed double-labeled retinal ganglion cells (DL RGCs) projecting to both nuclei. The soma-size distribution of DL RGCs was compared with three other distributions: DRN-projecting RGCs, LGN-projecting RGCs, and a large sample of RGCs labeled via the optic nerve with DiI. DL RGC soma diameters fell primarily within the mid-to-upper size range of all three distributions. DL RGCs may provide information to both nuclei concerning comparable aspects of light and visual stimulation via collateralized axons. 2003 Elsevier Science B.V. All rights reserved. Theme: Sensory systems Topic: Subcortical visual pathways
... Although the PVT receives afferents from a wide variety of sources (Cornwall and Phillipson, 1988), no retinal afferents to it have been described in rodents prior to the current study. The retinofugal projections and their terminal sites have been extensively studied in several mammalian species by means of anterograde axonal transport techniques (Ling et al., 1998;Costa et al., 1999;Fite et al., 1999;Fite and Janusonis, 2001). Although the basic organizational pattern of retinofugal projections is similar among mammalian species, a considerable variation has been pointed out in more recent studies. ...
... The retinal-PVT pathway may be associated with what has been described as the "non-image forming" subsystem of retinal afferents that includes the retino-hypothalamic projection to the SCN and other hypothalamic targets (Costa et al., 1999), as well as sparse retinal afferents to the piriform cortex and the olfactory tubercle (Mick et al., 1993), peri-amygdaloid area (Elliott et al., 1995), lateral habenular nucleus (Qu et al., 1996), dorsal raphe nucleus (Fite et al., 1999;Fite and Janusonis, 2001), and the parabrachial complex (Engelberth et al., 2008). Except the projection to the SCN, like present results, this non-image forming subset of retinal afferents consists of sparse projections, and may be involved in the photic regulation of arousal, neuroendocrine and circadian functions and they appear to encode the temporal, rather than spatial, characteristics of light stimulation. ...
The thalamic paraventricular nucleus (PVT) receives afferents from numerous brain areas, including the hypothalamic suprachiasmatic nucleus (SCN), considered to be the major circadian pacemaker. The PVT also sends projections to the SCN, limbic system centers and some nuclei involved in the control of the Sleep-Wake cycle. In this study, we report the identification of a hitherto not reported direct retinal projection to the PVT of the rock cavy, a typical rodent species of the northeast region of Brazil. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-immunoreactive fibers and presumptive terminals were seen in the PVT. Some possible functional correlates of the present data are briefly discussed, including the role of the PVT in the modulation of the circadian rhythms by considering the reciprocal connections between the PVT and the SCN. The present work is the first to show a direct retinal projection to the PVT of a rodent and may contribute to elucidate the anatomical substrate of the functionally demonstrated involvement of this midline thalamic nucleus in the modulation of the circadian timing system.
... Studies have shown that other "non-image-forming" areas receive direct retinal projections in several species [4,6,8,11,13,16,25,28,31,43,52]. Among these areas is the parabrachial complex (PB), located in an area surrounding the superior cerebellar peduncle [12]. ...
... It is likely that this complex, at least the neurons of the medial portion of the marmoset PB, is involved with some visual information processing. For rodents, there is a suggestion that this innervation represents an extension of the retinal fibers aimed to the raphe nuclei [11,13], which raises the conjecture of their meaning. In the marmoset, the retinal projection to the raphe complex was not yet reported. ...
Traditional retinal projections target three functionally complementary systems in the brain of mammals: the primary visual system, the visuomotor integration systems and the circadian timing system. In recent years, studies in several animals have been conducted to investigate the retinal projections to these three systems, despite some evidence of additional targets. The aim of this study was to disclose a previously unknown connection between the retina and the parabrachial complex of the common marmoset, by means of the intraocular injection of cholera toxin subunit b. A few labeled retinal fibers/terminals that are detected in the medial parabrachial portion of the marmoset brain show clear varicosities, suggesting terminal fields. Although the possible role of these projections remains unknown, they may provide a modulation of the cholinergic parabrachial neurons which project to the thalamic dorsal lateral geniculate nucleus.
... In many nocturnal animals, light reaches the raphe nuclei through a direct projection from the retina (Shen and Semba 1994;Kawano, Decker, and Reuss 1996;Fite and Janusonis 2001), while a direct projection in Arvicanthis has not been described (Adidharma, Leach, and Yan 2012;Gaillard, Karten, and Sauvé 2013). In diurnal animals, light signal reaching the serotonergic system may be modulated by other arousal structures, such as the orexinergic system, which is involved as well in regulating sleep and arousal (Kilduff and Peyron 2000). ...
In mammals, all rhythmic functions are orchestrated by the Suprachiasmatic nucleus (SCN), the master clock. While behavioral activity occurs at opposite phases in diurnal and nocturnal species, the SCN is always active at the same astronomical time. We investigated whether structures of the arousal system, namely the serotonergic (5HT) Raphe nuclei (RN) and noradrenergic (NA) Locus Coeruleus (LC), are involved in the opposite temporal organization between nocturnal and diurnal species. We showed that 5HT and NA synthesis, as well as clock gene expression in the RN and LC, are opposite between the diurnal Arvicanthis and the nocturnal rat, and correlate with their respective behavioral patterns. Furthermore, we showed that behavior enhances the SCN multi-unit activity (MUA) in Arvicanthis (in opposition to the rat), and that fluoxetine, a 5HT reuptake inhibitor, dampens the amplitude of both MUA and behavioral activity rhythms. These data show that the rhythmic functioning of arousal structures and their interactions with the SCN, is different between diurnal and nocturnal animals, and may participate to their different temporal organization.
... Finally, other light-dependent mechanisms may have an impact on tph2 expression. Light influences the 5HT system not only through the circadian system (e.g. via corticosterone rhythm), but also via other pathways [31,43,53].While in many rodent species, the DRN receives light information through direct projections from the retina [54][55][56], a similar direct projection has not been observed in Arvicanthis [57]. Thus, in Arvicanthis light information may be conveyed to the 5HT system through other structures of the arousal system. ...
In mammals, behavioral activity is regulated both by the circadian system, orchestrated by the suprachiasmatic nucleus (SCN), and by arousal structures, including the serotonergic system. While the SCN is active at the same astronomical time in diurnal and nocturnal species, little data are available concerning the serotonergic (5HT) system in diurnal mammals. In this study, we investigated the functioning of the 5HT system, which is involved both in regulating the sleep/wake cycle and in synchronizing the SCN, in a diurnal rodent, Arvicanthis ansorgei. Using in situ hybridization, we characterized the anatomical extension of the raphe nuclei and we investigated 24 h mRNA levels of the serotonin rate‐limiting enzyme, tryptophan hydroxylase 2 (tph2). Under both 12 h:12 h light/dark (LD) and constant darkness (DD) conditions, tph2 mRNA expression varies significantly over 24 h, displaying a bimodal profile with higher values around the (projected) light transitions. Furthermore, we considered several SCN outputs, namely melatonin, corticosterone, and locomotor activity. In both LD and DD, melatonin profiles display peak levels during the biological night. Corticosterone plasma levels show a bimodal rhythmic profile in both conditions, with higher levels preceding the two peaks of Arvicanthis locomotor activity, occurring at dawn and dusk. These data demonstrate that serotonin synthesis in Arvicanthis is rhythmic and reflects its bimodal behavioral phenotype, but differs from what has been previously described in nocturnal species.
... Une forte activation de cette région a été montrée suite à une stimulation lumineuse (Fite et al., 2005). De nombreuses espèces présentent une projection de la rétine sur ce noyau, elle est retrouvée chez le rat (Shen et Semba, 1994 ;Fite et al., 1999 ;Li et al., 2015), la gerbille de Mongolie (Fite et al., 1999 ;Luan et al., 2011), le chat (Foote et al., 1978), la musaraigne (Reuss et Fuchs, 2000), l'octodon (Fite et Janusonis, 2001) et le singe (Frazao et al., 2008). Chez la souris, cette projection semble très faible et à peine détectable . ...
Le traitement de la dépression reste insatisfaisant. Avec un tiers des patients ne répondant à aucun traitement proposé, un délai d’action long, et des effets secondaires non négligeables, la nécessité de développer de nouvelles stratégies thérapeutiques devient urgente. La luminothérapie, traitement de choix de la dépression saisonnière, a été montrée depuis une trentaine d’années comme présentant également un intérêt pour le traitement des dépressions non saisonnières, unipolaires comme bipolaires. Cependant, les mécanismes d’actions sous-tendant l’effet antidépresseur de la lumière restent mal connus. L’objectif de ce travail de thèse est de comprendre, à l’aide d’un modèle original de dépression, les mécanismes neurobiologiques à l’origine de l’effet antidépresseur de la lumière. Nous avons pour cela développé un modèle de dépression combinant stress par la nage forcée et isolation sociale. Nos résultats montrent que ce protocole induit chez les animaux des comportements pseudo-dépressifs stables et résistants à des traitements classiques (escitalopram) mais également à la kétamine, utilisée récemment en étude clinique pour traiter certains patients réfractaires. Si la lumière seule à forte irradiance (Bright light stimulation, BLS, 1000 lux, une heure par jour) n’a pas d’effet antidépresseur, nous avons démontré dans notre modèle de dépression résistante que la BLS permettait de potentialiser la réponse antidépressive d’une combinaison de kétamine et de scopolamine (utilisée récemment comme d’antidépresseur potentiel) à des doses sous-efficaces. Cet effet est modulé par la sérotonine. En effet, la déplétion en tryptophane, précurseur de la sérotonine, bloque l’effet antidépresseur de cette combinaison. De manière intéressante, nous avons découvert que l’effet potentialisateur de la lumière met en jeu les astrocytes de l’habénula latérale. Ces données suggèrent que la lumière associée à la kétamine et la scopolamine, ciblerait les astrocytes afin de rétablir une activité normale dans l’habénula latérale, désinhibant les centres monoaminergiques, menant ainsi à une réponse antidépressive. Ce travail a permis de mieux comprendre les mécanismes à l’origine de la potentialisation de l’effet antidépresseur par la lumière et pourrait aider à optimiser les stratégies thérapeutiques chez les patients déprimés résistants aux traitements incluant la kétamine
... This suggests that light can regulate mood independently of the master clock. The pattern of DRN innervation is similar across all species studied thus far; retinal fibers emerge from the optic tract at the level of the pretectum/anterior superior colliculus and descend into the PAG and terminate in the dorsomedial and lateral subdivisions of the DRN (Fite et al., 1999;Fite and Janusonis, 2001). The majority of these RGCs are described as having alpha-like morphological features and Y type visual response properties (Luan et al., 2011). ...
Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models. Finally, we provide evidence that 5-HT is a critical factor linking dysregulation of the circadian system and mood. Determining how these two systems interact may provide novel therapeutic targets for depression.
... During the past decade or so, an anatomical link has been identified between the retina and the DRN ("retino-raphe projection") in a number of rodent species. These species include the rat (177)(178)(179), the mouse (180); the Mongolian gerbil (179,181,182), and the Chilean degus (183). It has been shown that stimulation of this pathway by light can modulate the expression of cFos, an index of neuronal activity, in the DRN (182). ...
Pupil dilation is mediated by a sympathetic output acting in opposition to parasympathetically mediated pupil constriction. While light stimulates the parasympathetic output, giving rise to the light reflex, it can both inhibit and stimulate the sympathetic output. Light-inhibited sympathetic pathways originate in retina-receptive neurones of the pretectum and the suprachiasmatic nucleus (SCN): by attenuating sympathetic activity, they allow unimpeded operation of the light reflex. Light stimulates the noradrenergic and serotonergic pathways. The hub of the noradrenergic pathway is the locus coeruleus (LC) containing both excitatory sympathetic premotor neurones (SympPN) projecting to preganglionic neurones in the spinal cord, and inhibitory parasympathetic premotor neurones (ParaPN) projecting to preganglionic neurones in the Edinger-Westphal nucleus (EWN). SympPN receive inputs from the SCN via the dorsomedial hypothalamus, orexinergic neurones of the latero-posterior hypothalamus, wake- and sleep-promoting neurones of the hypothalamus and brain stem, nociceptive collaterals of the spinothalamic tract, whereas ParaPN receive inputs from the amygdala, sleep/arousal network, nociceptive spinothalamic collaterals. The activity of LC neurones is regulated by inhibitory α2-adrenoceptors. There is a species difference in the function of the preautonomic LC. In diurnal animals, the α2-adrenoceptor agonist clonidine stimulates mainly autoreceptors on SymPN, causing miosis, whereas in nocturnal animals it stimulates postsynaptic α2-arenoceptors in the EWN, causing mydriasis. Noxious stimulation activates SympPN in diurnal animals and ParaPN in nocturnal animals, leading to pupil dilation via sympathoexcitation and parasympathetic inhibition, respectively. These differences may be attributed to increased activity of excitatory LC neurones due to stimulation by light in diurnal animals. This may also underlie the wake-promoting effect of light in diurnal animals, in contrast to its sleep-promoting effect in nocturnal species. The hub of the serotonergic pathway is the dorsal raphe nucleus that is light-sensitive, both directly and indirectly (via an orexinergic input). The light-stimulated pathways mediate a latent mydriatic effect of light on the pupil that can be unmasked by drugs that either inhibit or stimulate SympPN in these pathways. The noradrenergic pathway has widespread connections to neural networks controlling a variety of functions, such as sleep/arousal, pain, and fear/anxiety. Many physiological and psychological variables modulate pupil function via this pathway.
... The DRN is the major area producing 5-HT for the forebrain, and is also one of the vital regions in response to light stimuli [55]. A retinal projection to the DRN has been found in many species, including cat [94], rat [95,96], Mongolian gerbil [96,97], tree shrew [98], Octodon degus [99], and the monkey Cebus apella [100]; but it is barely detectable in the mouse [48]. Light stimuli are able to significantly activate neuronal activity in the human brainstem through functional MRI detection [101], further based on the anatomical region of the human raphe [102], which suggests the existence of human retino-raphe circuitry. ...
Observations from clinical trials have frequently demonstrated that light therapy can be an effective therapy for seasonal and non-seasonal major depression. Despite the fact that light therapy is known to have several advantages over antidepressant drugs like a low cost, minimal side-effects, and fast onset of therapeutic effect, the mechanism underlying light therapy remains unclear. So far, it is known that light therapy modulates mood states and cognitive functions, involving circadian and non-circadian pathways from retinas into brain. In this review, we discuss the therapeutic effect of light on major depression and its relationship to direct retinal projections in the brain. We finally emphasize the function of the retino-raphe projection in modulating serotonin activity, which probably underlies the antidepressant effect of light therapy for depression.
... In addition to the retinoraphe pathway described in the cat (Foote et al., 1978), retinal afferent fibers have been reported to innervate the DRN in several mammalian species including the rat (Sprague Dawley and Wistar), Mongolian gerbil (Meriones unguiculatus), Chilean degus (Octodon degus), tree shrew (Tupaia belangeri) and a new world monkey (Cebus apella) (Shen and Semba, 1994;Kawano et al., 1996;Fite et al., 1999;Reuss and Fuchs, 2000;Fite and Janušonis, 2001;Frazão et al., 2008;Luan et al., 2011). A retinoraphe projection has not been observed following intraocular tracer injections in the golden hamster (Mesocricetus auratus), the California ground squirrel (Spermophilus beecheyi) or the Nile grass rat (Arvicanthis niloticus) (Major et al., 2003;Morin and Allen, 2006;Gaillard et al., 2013). ...
Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis-facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells.
... Degus have the potential for dichromatic color vision on the basis of green-sensitive M cones and UV-sensitive (in the near UV) S cones, the most common type of mammalian color vision (Jacobs, 1993;Chávez et al., 2003;Palacios-Muñoz et al., 2014). In degus, the retinal projection is primarily contralateral, with a small ipsilateral component (Fite and Janusonis, 2001). Degu is also well suited model for studying eye pathology, because they have an increased susceptibility to cataract development and aging (Worgul and Rothstein, 1975;Brown and Donnelly, 2001;Peichl et al., 2005). ...
The retina is sensitive to age-dependent degeneration. To find suitable animal models to understand and map this process has particular importance. The degu (Octodon degus) is a diurnal rodent with dichromatic color vision. Its retinal structure is similar to that in humans in many respects, therefore, it is well suited to study retinal aging. Histological, cell type-specific and ultrastructural alterations were examined in 6, 12 and 36 months old degus. The characteristic layers of the retina were present at all ages, but slightly loosened tissue structure could be observed in 36-month-old animals both at light and electron microscopic levels. Elevated glial fibrillary acidic protein expression was observed in Müller glial cells in aging retinas. The number of rod bipolar cells and the ganglion cells was reduced in the aging specimens, while that of cone bipolar cells remained unchanged. Other age-related differences were detected at ultrastructural level: alteration of the retinal pigment epithelium and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and often differed in morphology from those in the young animals. These results support our hypothesis that (i) the rod pathway seems to be more sensitive than the cone pathway to age-related cell loss; (ii) structural changes in the basement membrane of pigment epithelial cells can be one of the early signs of degenerative processes; (iii) the loss of synaptic proteins especially from those of the ribbon synapses are characteristic and (iv) the degu retina may be a suitable model for studying retinal aging.
... Data also showed that retinal ganglion cells projecting to the DRN are partially the same cells that project to the lateral geniculate complex of the thalamus (Fite, Birkett, Smith, Janušonis, & McLaughlin, 2003). In another rodent, Octodon degus, the retinal projection is concentrated in the dorsomedial and lateral portions of the DRN, with contralateral predominance (Fite & Janušonis, 2001). In Cebus apella, a New World primate, a direct retinal projection to the DRN was also described (Frazão et al., 2008). ...
All mammal behaviors and functions exhibit synchronization with environmental rhythms. This is accomplished through an internal mechanism that generates and modulates biological rhythms. The circadian timing system, responsible for this process, is formed by connected neural structures. Pathways receive and transmit environmental cues to the central oscillator, the hypothalamic suprachiasmatic nucleus, which mediates physiological and behavioral alterations. The suprachiasmatic nucleus has three major inputs: The retinohypothalamic tract (a direct projection from the retina), the geniculohypothalamic tract (an indirect photic projection originating in the intergeniculate leaflet), and a dense serotonergic plexus from the raphe nuclei. The serotonergic pathway, a source of non-photic cues to the suprachiasmatic nucleus, modulates its activity. The importance of raphe nuclei in circadian rhythms, especially in photic responses, has been demonstrated in many studies. Serotonin is the raphe neurotransmitter that triggers phase shifts, inhibits light-induced phase-shifts, and plays a role in controlling the sleep-wake cycle. All data to date have demonstrated the importance of the raphe, through serotonergic afferents, in adjusting circadian rhythms and must therefore be considered a component of the circadian timing system. The aim of this paper is to review the literature addressing the involvement of serotonin in the modulation of circadian rhythm.
... Its major function most probably is the modulation of pacemaker re- sponses to light. Since the raphe nuclei receive ret- inal afferents in rats, gerbils, tree shrews and Chi- lean degus [Fite et al., 1999;Reuss and Fuchs, 2000;Fite and Janusonis, 2001;Su and Liu, 2001], the raphe-retina projection may be re- garded as another indirect photic input to the clock. Previous retrograde tracing studies showed that the midbrain dorsal and median raphe nuclei (DRN, MRN) project to the SCN. ...
... In A. niloticus, retinohypothalamic projections innervate the SCN region and continue into the subparaventricular zone (Smale & Boverhof 1999) This region is likely to be critical for determining the active phase of diurnal and nocturnal rodents Moore & Danchenko 2002;Schwartz et al. 2004;Schwartz & Smale 2005;Ramanathan et al. 2006). The retinal projections to the dorsal raphe, an indirect pathway for light to affect the circadian system (Morin & Allen 2006), are considerably denser in some diurnal and crepuscular rodents compared to rats (Fite et al. 1999;Fite & Janusonis 2001). This feature is not apparent in other diurnal rodents, however (Major et al. 2003), and may reflect inter-species variability. ...
Diurnal animals occupy a different temporal niche from nocturnal animals and are consequently exposed to different amounts of light as well as different dangers. Accordingly, some variation exists in the way that diurnal animals synchronize their internal circadian clock to match the external 24-hour daily cycle. First, though the brain mechanisms underlying photic entrainment are very similar among species with different daily activity patterns, there is evidence that diurnal animals are less sensitive to photic stimuli compared to nocturnal animals. Second, stimuli other than light that synchronize rhythms (i.e. nonphotic stimuli) can also entrain and phase shift daily rhythms. Some of the rules that govern nonphotic entrainment in nocturnal animals as well as the brain mechanisms that control nonphotic influences on rhythms do not appear to apply to diurnal animals, however. Some evidence supports the idea that arousal or activity plays an important role in entraining rhythms in diurnal animals, either during the light (active) or dark (inactive) phases, though no consistent pattern is seen. GABAergic stimulation induces phase shifts during the subjective day in both diurnal and nocturnal animals. In diurnal Arvicanthis niloticus (Nile grass rats), SCN GABAA receptor activation at this time results in phase delays while in nocturnal animals phase advances are induced. It appears that the effect of GABA at this circadian phase results from the inhibition of period gene expression in both diurnal and nocturnal animals. Nonetheless, the resulting phase shifts are in opposite directions. It is not known what stimuli or behaviours ultimately induce changes in GABA activity in the SCN that result in alterations of circadian phase in diurnal grass rats. Taken together, studies such as these suggest that it may be problematic to apply the principles governing nocturnal nonphotic entrainment and its underlying mechanisms to diurnal species including humans.
... The DRN receives direct retinal projections in a few rodent species i.e. Mongolian gerbils, Chilean degus and lab rats [40,41,42,43]. However, no direct retinal projections were observed in the DRN of mice [44]. ...
Seasonal Affective Disorder (SAD) is one of the most common mood disorders with depressive symptoms recurring in winter when there is less sunlight. The fact that light is the most salient factor entraining circadian rhythms leads to the phase-shifting hypothesis, which suggests that the depressive episodes of SAD are caused by misalignments between the circadian rhythms and the habitual sleep times. However, how changes in environmental lighting conditions lead to the fluctuations in mood is largely unknown. The objective of this study is to develop an animal model for some of the features/symptoms of SAD using the diurnal grass rats Arvichantis niloticus and to explore the neural mechanisms underlying the light associated mood changes. Animals were housed in either a 12∶12 hr bright light∶dark (1000lux, BLD) or dim light∶dark (50lux, DLD) condition. The depression-like behaviors were assessed by sweet-taste Saccharin solution preference (SSP) and forced swimming test (FST). Animals in the DLD group showed higher levels of depression-like behaviors compared to those in BLD. The anxiety-like behaviors were assessed in open field and light/dark box test, however no significant differences were observed between the two groups. The involvement of the circadian system on depression-like behaviors was investigated as well. Analysis of locomotor activity revealed no major differences in daily rhythms that could possibly contribute to the depression-like behaviors. To explore the neural substrates associated with the depression-like behaviors, the brain tissues from these animals were analyzed using immunocytochemistry. Attenuated indices of 5-HT signaling were observed in DLD compared to the BLD group. The results lay the groundwork for establishing a novel animal model and a novel experimental paradigm for SAD. The results also provide insights into the neural mechanisms underlying light-dependent mood changes.
... As indicated, the retinorecipient IGL projects to most of the subcortical visual nuclei which, in turn, project back to the IGL, creating a variety of theoretical loops through which photic information might indirectly influence function of the SCN. It should also be noted, that among the convoluted pathways of the broader circadian visual system there is a direct visual projection to the dorsal raphe nucleus (DR) in several species, including the gerbil, degus, cat and rat (Foote, et al., 1978;Shen and Semba, 1994;Fite, et al., 1999;Fite and Janusonis, 2001), but has not been seen in the hamster (Morin and Blanchard, unpub. data). ...
The suprachiasmatic nucleus (SCN), site of the primary clock in the circadian rhythm system, has three major afferent connections. The most important consists of a retinohypothalamic projection through which photic information, received by classical rod/cone photoreceptors and intrinsically photoreceptive retinal ganglion cells, gains access to the clock. This information influences phase and period of circadian rhythms. The two other robust afferent projections are the median raphe serotonergic pathway and the geniculohypothalamic (GHT), NPY-containing pathway from the thalamic intergeniculate leaflet (IGL). Beyond this simple framework, the number of anatomical routes that could theoretically be involved in rhythm regulation is enormous, with the SCN projecting to 15 regions and being directly innervated by about 35. If multisynaptic afferents to the SCN are included, the number expands to approximately brain 85 areas providing input to the SCN. The IGL, a known contributor to circadian rhythm regulation, has a still greater level of complexity. This nucleus connects abundantly throughout the brain (to approximately 100 regions) by pathways that are largely bilateral and reciprocal. Few of these sites have been evaluated for their contributions to circadian rhythm regulation, although most have a theoretical possibility of doing so via the GHT. The anatomy of IGL connections suggests that one of its functions may be regulation of eye movements during sleep. Together, neural circuits of the SCN and IGL are complex and interconnected. As yet, few have been tested with respect to their involvement in rhythm regulation.
... The DRN is heavily innervated by orexin neurons in nocturnal lab rats (Peyron et al., 1998) and in diurnal grass rats (Nixon and Smale, 2007;present study). Although direct retinal projections in DRN have been reported in a few rodent species including Mongolian gerbils, Chilean degus and lab rats (Shen and Semba, 1994;Kawano et al., 1996;Fite et al., 1999;Fite and Janusonis, 2001), we have not observed any retinal innervations in the DRN of the grass rats (Shuboni et al., unpublished results). This is consistent with the results showing no projection from melanopsin-containing retinal ganglion cells in DRN in mice (Hattar et al., 2006). ...
Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos protein as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy.
... Therefore innervation of the DRN by Y (alpha) RGCs is both a novel observation and quite unexpected. RGCs have been shown to innervate the DRN in several mammalian species including the cat [2], rat [3,39,4], Chilean degus [40], tree shrew [41], and mongolian gerbil [4,5]. However, little is known about the morphology and physiology of RGCs projecting to DRN. ...
The dorsal raphe nucleus (DRN) of the mesencephalon is a complex multi-functional and multi-transmitter nucleus involved in a wide range of behavioral and physiological processes. The DRN receives a direct input from the retina. However little is known regarding the type of retinal ganglion cell (RGC) that innervates the DRN. We examined morphological characteristics and physiological properties of these DRN projecting ganglion cells.
The Mongolian gerbils are highly visual rodents with a diurnal/crepuscular activity rhythm. It has been widely used as experimental animals of various studies including seasonal affective disorders and depression. Young adult gerbils were used in the present study. DRN-projecting RGCs were identified following retrograde tracer injection into the DRN, characterized physiologically by extracellular recording and morphologically after intracellular filling. The result shows that DRN-projecting RGCs exhibit morphological characteristics typical of alpha RGCs and physiological response properties of Y-cells. Melanopsin was not detected in these RGCs and they show no evidence of intrinsic photosensitivity.
These findings suggest that RGCs with alpha-like morphology and Y-like physiology appear to perform a non-imaging forming function and thus may participate in the modulation of DRN activity which includes regulation of sleep and mood.
... 5-HT fibers from the MRN facilitating the synchronization of the animal to the light-dark cycle and the disruption of the DRN-IGL do not influence this response [22]. The reception of photic information by the raphe mesencephalic complex through the retinal projections is well characterized and fully recognized in some species [9][10][11] attributing to this system a pivotal role for 5-HT in circadian rhythmicity by indirect modulation in response to light [23,27,28]. Furthermore, some data show that the function of 5-HT in circadian rhythmicity goes beyond the light response. ...
Serotonin (5-HT) is involved in the fine adjustments at several brain centers including the core of the mammal circadian timing system (CTS) and the hypothalamic suprachiasmatic nucleus (SCN). The SCN receives massive serotonergic projections from the midbrain raphe nuclei, whose inputs are described in rats as ramifying at its ventral portion overlapping the retinohypothalamic and geniculohypothalamic fibers. In the SCN, the 5-HT actions are reported as being primarily mediated by the 5-HT1 type receptor with noted emphasis for 5-HT(1B) subtype, supposedly modulating the retinal input in a presynaptic way. In this study in a New World primate species, the common marmoset (Callithrix jacchus), we showed the 5-HT(1B) receptor distribution at the dorsal SCN concurrent with a distinctive location of 5-HT-immunoreactive fibers. This finding addresses to a new discussion on the regulation and synchronization of the circadian rhythms in recent primates.
... The retinofugal projections and their terminal sites have been extensively studied in several mammalian species by means of anterograde axonal transport techniques [8,13,14,32]. Although the basic organizational pattern of retinofugal projections is similar among mammalian species, a considerable variation has been pointed out in more recent studies. ...
The MD has reciprocal connections with the ventromedial prefrontal cortex (PFC) and with limbic cortices and appears to participate in learning and memory-related processes. In this study, we report the identification of a hitherto not reported direct retinal projection to the MD of the rock cavy, a typical rodent species of the Northeast region of Brazil. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-imunoreactive fibers and presumptive terminals were seen in the MD. A few labeled retinal fibers/terminals detected in the MD of the rock cavy brain show clear varicosities, suggesting terminal fields. The present work is the first to show a direct retinal projection to the MD of rodents and may contribute for elucidating the anatomical substrate of the functional involvement of this thalamic nucleus in the modulation of the visual recognition, emotional learning and object-reward association memory.
... In mammals, different components of the known, RITC does not appear to be taken up by distant or dorsal raphe nucleus have been linked to a number of neighboring axon terminals through leakage out of cennonperceptual effects of light and more specifically associtrifugal cells and subsequent diffusion in the extracellular ated with the photic regulation of arousal, neuroendocrine space. Consequently, within the ION, the tracer might have and circadian functions, sleep-wake states in addition to been taken up solely by those terminals which possess being involved in the effects of stressful stimulation synaptic contacts directly upon centrifugal cells and not by [8,9,18,33]. Further work will be required to determine the those distant axon terminals of afferent 5-HT-ir neurons manner in which the connections between the ION cellular involved in volume transmission. ...
Serotonin (5-HT) immunoreactive (-ir) profiles within the isthmo-optic nucleus (ION) of the centrifugal visual system (CVS) were studied in the pigeon using light microscopic immunohistofluorescent and electron microscopic immunocytochemical pre-embedding techniques. The brainstem origin of the 5-HT input upon the ION was determined by combining 5-HT immunohistofluorescence (FITC) and retrograde transneuronal tracing after intraocular injection of Rhodamine beta-isothiocyanate. The light microscopic results showed that 5-HT endings were mainly localised within the neuropillar zones of the ventral ION. The 5-HT-ir cell bodies, belonging to a lateral extension of the dorsal raphe system, were observed within the same region as the centrifugal ectopic neurons (EN) underlying the ION and some displayed dendritic processes which penetrated the nucleus. Double-labeled neurons, representing 5-HT-ir afferents to the ION, were identified only within the n. linearis caudalis region of the ventral raphe. The electron microscopic results confirmed the presence of 5-HT-ir dendritic processes within the ventral part of the nucleus and showed that they were contacted by axon terminals belonging to intrinsic interneurons. The functional organisation of the ION and the possible contribution of serotonergic raphe afferents and efferents are discussed in relation to present hypotheses linking the avian CVS to mechanisms of visual attention.
... The current study has confirmed sparse to moderate ipsilateral retinal projections to every retinorecipient structure and has confirmed such small projections as the retinal-anterodorsal tract. A projection to the dorsal raphe, reported for the cat (Foote et al., 1978) and for various rodents (Shen and Semba, 1994;Fite et al., 1999;Fite and Janusonis, 2001), was not observed in the ground squirrel. Reuss and Fuchs (2000) reported a projection to the dorsal raphe for the tree shrew, but the projection as depicted appears extremely sparse at best. ...
The retinofugal pathways in the California ground squirrel, Spermophilus beecheyi, were mapped after intravitreal injections of cholera toxin B-subunit. The results of the current study are consistent with work in other mammals and provide new details relevant to the organization and evolution of the visual system. All retinorecipient nuclei received bilateral input, with a contralateral predominance. The suprachiasmatic nucleus is heavily innervated, and sparse terminals were noted in other hypothalamic areas. In addition to the interstitial, medial, lateral, and dorsal terminal nuclei, a few fibers of the accessory optic tract may enter the ventral lateral geniculate and the nucleus of the optic tract, though this innervation may not derive from the same ganglion cells innervating the accessory optic nuclei. Retinal terminals are found in the intergeniculate leaflet and the "dorsal cap" of the ventral lateral geniculate. Retinal fibers pass rostrally from the dorsal cap toward the anterodorsal thalamus, confirming a projection described in the tree shrew and monkeys. Retinal termination patterns in the dorsal lateral geniculate reveal a hexilaminate organization of alternating ipsilateral and contralateral input. Variations in terminal morphology suggest that sublayers receive input from distinct ganglion cell types and that laminar comparisons can be made with primates. Finally, terminal patterns in the superior colliculus reveal a dense, highly ordered columnar organization supporting functional properties of tectal receptive fields. All the visual structures in the ground squirrel are large and well differentiated, making the sciurid visual system an accessible rodent model for comparing visual processing with that in other diurnal vertebrates.
... This projection includes both serotonergic and nonserotonergic neurons that may contribute to circadian rhythm regulation. This nucleus has also been implicated in visual system functioning to the extent that it receives direct retinal projections in several species (Foote et al., 1978;Shen and Semba, 1994;Fite et al., 1999;Fite and Janusonis, 2001), although apparently not in the hamster (Blanchard and Morin, unpublished data; K. Fite, personal communication). ...
The intergeniculate leaflet (IGL) has widespread projections to the basal forebrain and visual midbrain, including the suprachiasmatic nucleus (SCN). Here we describe IGL-afferent connections with cells in the ventral midbrain and hindbrain. Cholera toxin B subunit (CTB) injected into the IGL retrogradely labels neurons in a set of brain nuclei most of which are known to influence visuomotor function. These include the retinorecipient medial, lateral and dorsal terminal nuclei, the nucleus of Darkschewitsch, the oculomotor central gray, the cuneiform, and the lateral dorsal, pedunculopontine, and subpeduncular pontine tegmental nuclei. Intraocular CTB labeled a retinal terminal field in the medial terminal nucleus that extends dorsally into the pararubral nucleus, a location also containing cells projecting to the IGL. Distinct clusters of IGL-afferent neurons are also located in the medial vestibular nucleus. Vestibular projections to the IGL were confirmed by using anterograde tracer injection into the medial vestibular nucleus. Other IGL-afferent neurons are evident in Barrington's nucleus, the dorsal raphe, locus coeruleus, and retrorubral nucleus. Injection of a retrograde, trans-synaptic, viral tracer into the SCN demonstrated transport to cells as far caudal as the vestibular system and, when combined with IGL injection of CTB, confirmed that some in the medial vestibular nucleus polysynaptically project to the SCN and monosynaptically to the IGL, as do cells in other brain regions. The results suggest that the IGL may be part of the circuitry governing visuomotor activity and further indicate that circadian rhythmicity might be influenced by head motion or visual stimuli that affect the vestibular system.
... In rats, the superior colliculus and the lateral geniculate nucleus receive projections from neurons located in the lateral wings of the DRN, whereas neurons projecting to the primary visual cortex are primarily located in the ventromedial portions of the DRN [1,2,11]. In addition, a direct retinal projection to the DRN has been demonstrated recently in several mammalian species, with retinal axonal terminals distributed heterogeneously in different DRN subdivisions [12,13]. The functional significance of this direct retinal pathway is not known, although it appears to be well placed to mediate the effects of visual and environmental light stimulation on a broad range of behavioral, arousal, and affective states, some of which are affected in depressed patients with abnormalities in specific DRN subdivisions [14]. ...
The mammalian dorsal raphe nucleus (DRN) is composed of sub-divisions with different anatomical and functional properties. Using cholera toxin subunit B as a retrograde tracer, DRN subdivisions projecting to the lateral geniculate nucleus and to the primary visual cortex were examined in the Mongolian gerbil. DRN neurons projecting to the lateral geniculate nucleus were observed in the lateral DRN (rostrally) and in the ventromedial DRN (caudally), while DRN cells projecting to the primary visual cortex were observed at all rostral-caudal levels in the ventromedial DRN. These results demonstrate a significant overlap between the DRN projections to the lateral geniculate and superior colliculus, and show that only the caudal ventromedial DRN projects to all three major visual targets: the lateral geniculate nucleus, primary visual cortex, and superior colliculus. Since the DRN is involved in depression and other neuropsychiatric disorders, as well as is affected by many psychotropic substances, these data may help to develop new treatments and therapies targeting specific DRN subdivisions.
... Information about retinal illumination can be conveyed to the Hb via a direct projection from the retina (Reuss and Decker, 1997;Qu et al., 1996) and indirect connections from the SCN, raphe nuclei and pineal gland. The raphe nuclei themselves receive a direct retinal projection in several species (Shen and Semba, 1994;Fite et al., 1999;Reuss and Fuchs, 2000;Fite and Janusonis, 2001), and project to two key structures in the circadian system, the SCN and IGL (Meyer-Bernstein and Morin, 1996). The Hb is thus positioned to receive photic input both directly and from most structures known to be involved in circadian photic entrainment. ...
The suprachiasmatic nuclei of the anterior hypothalamus serve as the principal pacemaker of the mammalian circadian system. Among its efferent targets are the habenular nucleus (Hb), especially the lateral Hb (LHb), which plays an important role in conveying input from the limbic forebrain to midbrain structures. We recorded extracellularly from single neurons in the LHb and medial Hb (MHb), both in vivo and using an in vitro slice preparation, to assess their responses to retinal illumination and the rhythmicity of their firing rates. Of cells recorded in the LHb, 42% were tonically activated or suppressed by retinal illumination, while significantly fewer cells recorded in the MHb responded to retinal illumination (19%). Of photically responsive cells, 68% in the LHb were activated and the remainder suppressed, while only 25% of those recorded in the MHb were activated. Cells in both the LHb and MHb showed higher baseline firing rates during the day than during the night in vivo, while photic responses were of significantly larger amplitude among LHb cells during the projected night than during the projected day. LHb cells recorded in vitro maintained their rhythmicity for two circadian cycles, but MHb cells did not show a rhythm in vitro. The habenula may play a role in linking circadian and motivational systems and may contribute to photic regulation of these systems, as well as to the rhythmicity of their function.
... Interest was further heightened with the demonstration, based on both anterograde and retrograde tracing data, of a similar pathway in rat (Shen and Semba, 1994). This pathway has also been observed in gerbil (Fite et al., 1999Fite et al., , 2003) and O. degus (Fite and Janusonis, 2001). The pathway has not been found in hamster, although it has been sought several times (Morin and Blanchard, unpublished data; Fite, unpublished data). ...
The primary mammalian circadian clock resides in the suprachiasmatic nucleus (SCN), a recipient of dense retinohypothalamic innervation. In its most basic form, the circadian rhythm system is part of the greater visual system. A secondary component of the circadian visual system is the retinorecipient intergeniculate leaflet (IGL) which has connections to many parts of the brain, including efferents converging on targets of the SCN. The IGL also provides a major input to the SCN, with a third major SCN afferent projection arriving from the median raphe nucleus. The last decade has seen a blossoming of research into the anatomy and function of the visual, geniculohypothalamic and midbrain serotonergic systems modulating circadian rhythmicity in a variety of species. There has also been a substantial and simultaneous elaboration of knowledge about the intrinsic structure of the SCN. Many of the developments have been driven by molecular biological investigation of the circadian clock and the molecular tools are enabling novel understanding of regional function within the SCN. The present discussion is an extension of the material covered by the 1994 review, "The Circadian Visual System."
... tracers and therefore are candidates for cells of origin of the retinopetal axons. [3][4][5][6][7] Serotonergic axons are found in mouse optic nerves, 8 and after preincubation of rat retinas in serotonin, axons are labeled with antibodies against serotonin. 6,9 Furthermore, after electrolytic lesions 3 or injections of an indoleamine that destroys serotonergic neurons 10 in the dorsal raphe of rats, retinal serotonin levels are reduced. ...
To describe serotonergic retinopetal axons in monkeys.
Whole macaque and baboon retinas, fixed in 4% paraformaldehyde, were labeled with antisera raised against serotonin (5-HT).
Several large-diameter 5-HT-immunoreactive (IR) axons emerged from the optic disk. Most axons ran to the peripheral retina, where they branched extensively. Most terminated in the ganglion cell layer, but a few 5-HT-IR axons terminated in distal inner plexiform or within inner nuclear layer. Some axons branched extensively near the fovea, and a dense plexus of 5-HT-IR axons was also found around the optic disk. Varicose 5-HT-IR axons were also associated with blood vessels, especially in the central retina.
Immunoreactive serotonin is present in a distinct population of retinopetal axons in the monkey retina. Receptors for serotonin are present in the primate retinas, and based on physiological studies in other mammals, these retinopetal axons are expected to modulate neuronal activity and regulate blood flow.
... In a number of systematically widespread species, apparent centrifugal visual neurons are located either in structures close to the primary visual centres (Fig. 5), such as the thalamic and pretectal retinopetal nuclei described in some Teleostei Ekström, 1984;Meyer et al., 1989;Meyer et al., 1993;Northcutt and Butler, 1991;Repérant et al., 2006;Uchiyama, 1989), Caudata (Fritzsch and Himstedt, 1981) and Eutheria (Itaya, 1980;Itaya and Itaya, 1985;Labandeira-Garcia, 1988;Labandeira-Garcia et al., 1990;Mikkelsen, 1992), or in primary visual centres themselves; these include the superficial layers of the optic tectum of Elasmobranchii (Luiten, 1981), some Teleostei Meyer, 1981, 1989;Ekström, 1984;Schmidt, 1979) and its homologue the mammalian anterior colliculus (Larsen and Møller, 1985), the suprachiasmatic nucleus in Microcebus (Bons and Petter, 1986), the dorsal geniculate nucleus of the gerbil (Larsen and Møller, 1985), and the nucleus of the raphé in the mouse, rat and gerbil (Fite et al., 1996(Fite et al., , 1997Repérant et al., 2000;Villar et al., 1987), in which the retinal projections have been recently described (Fite and Janušonis, 2001;Fite et al., 1996Fite et al., , 1997Fite et al., , 1999Kawano et al., 1996;Shen and Semba, 1994). It is therefore conceivable, in spite of the absence of more formal proof, that these retinopetal neurons are also implicated in feedback loops . ...
In a recent review of the available data concerning the centrifugal visual system (CVS) of vertebrates [Repérant, J., Ward, R., Miceli, D., Rio, J.P., Médina, M., Kenigfest, N.B., Vesselkin, N.P., 2006. The centrifugal visual system of vertebrates: a comparative analysis of its functional anatomical organization, Brain Res. Rev. 52, 1-57], we have shown that this feature of the visual system is not a particularity of birds, but is a permanent component of the vertebrate central nervous system which nevertheless shows considerable morphological and functional variation from one taxonomic group to another. Given these findings, the primary objective of the present article is an attempt to specify the evolutionary significance of this phylogenetic diversity. We begin by drawing up an inventory of this variation under several headings: the intracerebral location of the retinopetal neurons; the mode of intra-retinal arborizations of the centrifugal fibres and the nature of their targets; their neurochemical properties; and the afferent supplies of these neurons. We subsequently discuss these variations, particularly that of the intracerebral location of the retinopetal neurons during development and in adult forms, using the neuromeric terminology and in the framework of cladistic analysis, and seek to interpret them in a phylogenetic context. From this analysis, it becomes evident that the CVS is not a homogeneous entity formed by neurons with a common embryological origin, but rather a collection of at least eight distinct subsystems arising in very different regions of the neuraxis. These are the olfacto-retinal, dorsal thalamo-retinal, ventral thalamo-retinal, pretecto-retinal, tecto-retinal, tegmento-mesencephalo-retinal, dorsal isthmo-retinal and ventral isthmo-retinal systems. The olfacto-retinal system, which is probably absent in Agnatha, appears to be a pleisiomorphic characteristic of all Gnathostomata, while on the other hand the tegmento-mesencephalo-retinal system appears to be present only in Agnatha. Our cladistic analysis also shows that the remaining six subsystems are polyphyletic in origin and have arisen independently on several occasions in different radiations of Gnathostoma. In conclusion, we suggest that, in the course of the palaeontological history of vertebrates, these different retinopetal pathways have been selected on the basis of widely different environmental pressures which remain to be identified.
Light profoundly affects the behavior and physiology of almost all animals, including humans. One such effect in humans is that the level of illumination during the day positively contributes to affective well-being and cognitive function. However, the neural mechanisms underlying the effects of daytime light intensity on affect and cognition are poorly understood. One barrier for progress in this area is that almost all laboratory animal models studied are nocturnal. There are substantial differences in how light affects nocturnal and diurnal species, e.g., light induces sleep in nocturnal mammals and wakefulness in diurnal ones, like humans. Therefore, the mechanisms through which light modulates affect and cognition must differ between the chronotypes. To further understand the neural pathways mediating how ambient light modulates affect and cognition, our recent work has developed a diurnal rodent model, the Nile grass rat (Arvicanthis niloticus), by chronically manipulating daytime light intensity in grass rats housed under the same 12:12 hour light/dark cycle. This simulates lighting conditions during summer-like bright sunny days vs. winter-like dim cloudy days. Our work has revealed that chronic dim daylight intensity results in higher depression- and anxiety-like behaviors, as well as impaired spatial learning and memory. Furthermore, we have found that hypothalamic orexin is a mediator of these effects. A better understanding of how changes in daytime light intensity impinge upon the neural substrates involved in affect and cognition will lead to novel preventive and therapeutic strategies for seasonal affective disorder, as well as non-seasonal emotional or cognitive impairments associated with light deficiency.
Light emitting diodes (LEDs) possess advantages to be applied as one of the key medical devices in the field of phototherapy. In this paper, effects of blue light on inducing sleep have been examined based on the experiments for 100 test subjects. Narrow-band (<11 nm in full width of half maximum in the emission spectrum) irradiation was found to be more effective for inducing sleep. It should be noted that the intensity of light employed in this study was far less that that suppressing the secretion of melatonin and obstructing the circadian rhythm, which has recently extended widely. Since a variety of light sources in terms of wavelengths, bandwidths, and intensity are required in the medical applications or light therapy, LEDs are the ideal device and the efforts of developing new LEDs with the materials research of semiconductors are strongly demanded.
The dorsal raphe nucleus (DRN) is a major serotonin (5-hydroxytryptamine, 5-HT)-producing region in the central nervous system. It receives glutamatergic inputs from several brain regions, which are reciprocally modulated by serotonergic signals. We investigated whether serotonin 5-HT4 receptors (5-HT4Rs) play a role in the development of glutamatergic control of the DRN, with an emphasis on cortical inputs. Double-label immunohistochemistry and confocal microscopy were used to quantify vesicular glutamate transporter 1 (vGluT1)-immunoreactive terminals in the DRN of mice with a null-mutation in the 5-HT4R gene. We found no significant change in the overall density of vGluT1-positive terminals in homozygous and heterozygous mice, but heterozygous mice had a significantly higher density of vGluT1-positive terminals contacting serotonergic neurons. These results suggest that altered 5-HT4R expression may affect the development of cortical glutamatergic control of the DRN.
Purpose:
A retinal projection into the dorsal raphe nucleus (DRN), namely, the retino-raphe projection, exists in many species. The rat is one of several species in which a retino-raphe projection has been described; however, the retinal ganglion cell (RGC) types that contribute to this pathway are unknown.
Methods:
Retrograde tracing via cholera toxin subunit B (CTB) was used to reveal DRN-projecting RGCs in rats, combined with intracellular injection in vitro, melanopsin immunostaining in whole-mounted retinas, and serotonin immunostaining to define the DRN. We modified methods of CTB injection into DRN used previously in order to avoid possible contamination with other retinorecipient regions, particularly the superior colliculus (SC).
Results:
The majority of DRN-projecting RGCs showed alpha-like morphology, and some CTB-positive RGCs were colabeled with melanopsin. Approximately 80% of the total population of CTB-labeled DRN-projecting RGCs was alpha-like cells including ON alpha cells and OFF alpha cells; these alpha-like cells were melanopsin immunonegative. Approximately 10% of the remaining DRN-projecting RGCs were melanopsin immunopositive, in which the M1 subtype of intrinsically photosensitive retinal ganglion cell (ipRGC) provided the dominant projection of ipRGCs into DRN, with only few non-M1 ipRGCs involved. The DRN-projecting ipRGCs could be retrogradely labeled following tracer injection into all rostrocaudal aspects of the DRN.
Conclusions:
Both conventional RGCs with alpha-like morphology and melanopsin-expressing ipRGCs project into the rat DRN. Approximately 10% of DRN-projecting RGCs were colabeled with melanopsin, and the majority of these were the M1 subtype of ipRGCs. An ipRGC component of the retino-raphe projection may contribute to a sustained light-mediated modulation of DRN serotonin release.
The projections from the dorsal raphe (DR) to the locus coeruleus (LC) or vice versa were analyzed in the rat using an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA‐L) combined with serotonin (5‐hydroxytryptamine, 5‐HT) or dopamine‐beta‐hydroxylase (DBH) immunostaining. Following the injection of PHA‐L into the middle DR, DR‐originating fibers with varicosities have contacted DBH‐immunolabeled cells in the rostral, middle, and caudal LC. Axon terminals were also observed in the subcoeruleus nucleus. When the PHA‐L injection was confined within the caudal DR, axonal fibers with varicosities were observed mainly at the rostral pole of the LC. Following the injection of PHA‐L into the caudal, principal LC, labeled fibers with varicosities have contacted 5‐HT‐immunolabeled neurons at dorsomedial, ventromedial, lateral wing, and caudal sub‐divisions of the DR. The present anterograde study suggests that the DR or the LC nuclei communicate with each other in order to perform a variety of functions including vigilance, analgesia, and stress responses.
The Nile grass rat (Arvicanthis niloticus) has a high proportion of cone photoreceptors (≈30-40%) compared to that in the common laboratory mouse and rat (≈1-3%), and may prove a preferable murine model to study cone-driven information processing in retina and primary visual centers. However, other than regions involved in circadian control, little is known on retinorecipient structures in this rodent. We undertook a detailed analysis of the retinal projections as revealed after intravitreal injection of the anterograde tracer cholera toxin subunit B. Retinal efferents were evaluated in 45 subcortical structures. Contralateral projections were always dominant. Major contralateral inputs consisted of the suprachiasmatic nucleus, dorsolateral geniculate nucleus (dLGN), intergeniculate leaflet, ventral geniculate nucleus (magnocellular part), lateroposterior thalamic nucleus, all six pretectal nuclei, superficial layers of the superior colliculus (SC) and the main nuclei of the accessory optic system. Terminals from the contralateral eye were also localized in an unnamed field rostromedial to the dLGN as well as in the subgeniculate thalamic nucleus. Ipsilateral inputs were mainly found in the suprachiasmatic nucleus, dLGN, intergeniculate leaflet, internal sector of the magnocellular part of the ventral geniculate nucleus, olivary pretectal nucleus and SC optic layer. Retinal afferents were not detected in the basal forebrain or the dorsal raphe nucleus. Morphometric measurements revealed that the superficial layers of the SC are disproportionately enlarged relative to other retinorecipient regions and brain size when compared to rats and mice. We suggest that this reflects the selective projection of cone-driven retinal ganglion cells to the SC. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc.
The Octodon degus, or degu, is an excellent animal model for studying the theoretical and neural underpinnings of diurnality. The power of this model comes from their unique evolutionary lineage, long lives, and relative ease of care in the laboratory for a non-domesticated species. We have summarized the field and laboratory data indicating the critical variables that influence the degus' phase preference and the possible mechanisms for the phase flexibility observed in the field and laboratory. We also review studies examining the physiology and anatomy of light and non-photic inputs to the degu circadian system and studies of the circadian pacemaker itself, with particular emphasis placed on characteristics that appear to be convergent adaptations to a diurnal niche. Finally, we begin to seek the origin for the diurnally-phased activity output of the degu, although we conclude that significant work remains to be done.
Recent studies suggest that the dorsal raphe nucleus (DRN) of the brainstem contains several subdivisions that differ both anatomically and neurochemically. The present study examined whether variation of c-Fos expression across the 24-hour light-dark cycle may also be different in these subdivisions. Animals were kept on a 12:12 light-dark cycle, were perfused at seven different time points, and brain sections were processed by using c-Fos immunocytochemistry. At all coronal levels of the DRN, c-Fos expression reached a peak 1 hour after the light-dark transition (lights-off) and reached its lowest levels in the middle of the light period. In contrast to the light-dark transition, c-Fos levels did not change significantly after the dark-light transition (lights-on). One-way analysis of variance (ANOVA) revealed that the diurnal variation of c-Fos expression was highly significant in the caudal ventral DRN. Similar variation in c-Fos expression also was observed in the other DRN subdivisions, but this variation appeared to gradually diminish in the caudal-to-rostral and ventromedial-to-dorsomedial directions. Double-label immunocytochemistry revealed that, 1 hour after lights-off, only 11% of c-Fos-positive neurons in the caudal ventral DRN were serotonin (5-HT)-immunoreactive. These results suggest that DRN subdivisions may differ functionally with regard to the diurnal cycle, and that these differences may be reflected in the activity of nonserotonergic cells in the DRN. J. Comp. Neurol. 440:31–42, 2001. © 2001 Wiley-Liss, Inc.
Injections of rhodamine-B into the dorsal raphe nucleus (DRN) and Fluoro-Gold into the lateral geniculate nucleus (LGN) revealed double-labeled retinal ganglion cells (DL RGCs) projecting to both nuclei. The soma-size distribution of DL RGCs was compared with three other distributions: DRN-projecting RGCs, LGN-projecting RGCs, and a large sample of RGCs labeled via the optic nerve with DiI. DL RGC soma diameters fell primarily within the mid-to-upper size range of all three distributions. DL RGCs may provide information to both nuclei concerning comparable aspects of light and visual stimulation via collateralized axons.
The interconnection between two brainstem monoaminergic nuclei, the dorsal raphe (DR) and the locus coeruleus (LC), was analyzed in the rat using retrograde tracing and immunocytochemistry. Gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) was injected into subdivisions of the DR or rostro-caudal levels of the nuclear core of the LC, and labeled LC or DR neurons were identified by dopamine-beta-hydroxylase (DBH) or 5-hydroxytryptamine (5-HT) immunostaining, respectively. Within the LC-DR projection, the caudal principal LC projected to the caudal, ventromedial, and interfascicular DR. Mid-LC as well as caudal LC projected with an ipsilateral predominance to the lateral wing subdivision of the DR. A few rostral LC neurons projected to caudal, dorsomedial, and ventromedial DR. Within the DR-LC projection, the rostral LC received inputs mainly from the caudal, dorsomedial, and ventromedial DR. Mid-LC to caudal LC received projections from mid-DR to caudal DR, with the heaviest projection from the ipsilateral lateral wing as well as caudal DR. The DR-LC projection was substantially more robust than LC-DR and included both serotonergic and nonserotonergic components. Thus, the data demonstrate topographically ordered, reciprocal connectivity between DR and LC with particularly strong projections from DR to LC. Communication between these two brainstem monoaminergic nuclei may be critical for a variety of functions including sleep-wake regulation, vigilance, analgesia, cognition, and stress responses.
The effect of light on neuroendocrine functions is thought to be mediated through retinal inputs to the circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). The present studies were conducted to provide experimental evidence for this signaling modality in non-human primates. In the St. Kitts vervet monkey, anterograde tracing of SCN efferents revealed a monosynaptic pathway between the circadian clock and hypothalamic neurons producing luteinizing hormone-releasing hormone (LHRH). Using a variety of tracing techniques, direct retinal input was found to be abundant in the SCN and in other hypothalamic sites. Strikingly, in hypothalamic areas other than the SCN, primary visual afferents established direct contacts with neuroendocrine cells including those producing LHRH and dopamine, neurons that are the hypothalamic regulators of pituitary gonadotrops and prolactin. Thus, our data reveal for the first time in primates that light stimuli can reach the hypothalamo-pituitary-gonadal axis, directly providing a pathway independent of but parallel to that of the circadian clock for the photic modulation of hormone release.
Retinal afferents to the dorsal raphe nucleus (DRN) have been described in a number of species, including Mongolian gerbils, but functional correlates of this optic pathway are unknown at present. To determine whether temporally modulated photostimulation can affect c-Fos expression in the gerbil DRN, quantitative analysis of c-Fos-immunoreactive (c-Fos-ir) neurons was conducted following 60-min exposure to pulsed (2 Hz) photostimulation at selected times over the 12:12 h light/dark cycle. For comparison, c-Fos expression was also analyzed in the subnuclei of the lateral geniculate complex and in the suprachiasmatic nucleus (SCN). In the DRN, a substantial reduction was observed in the number of c-Fos immunoreactive (c-Fos-ir) neurons during the light period and early dark period in photostimulated vs. control animals. Similar results were obtained in the intergeniculate leaflet (IGL) and ventral lateral geniculate (VLG). However, no significant changes were observed in the number of c-Fos-ir neurons in the dorsal lateral geniculate nucleus or suprachiasmatic nucleus (SCN) following photostimulation, except for an increase in the middle of the dark period. These findings indicate that photic stimulation can lead to a suppression or down-regulation of c-Fos expression in the DRN that is probably mediated via the direct retinal pathway to the DRN in this species. The similarity between c-Fos expression profiles in the DRN and IGL/VGL suggest that efferent projections from the DRN may modulate c-Fos expression to visual stimulation in these subnuclei of the lateral geniculate complex.
Serotonin (5-HT) immunostained sections were analyzed using integrated optical density (IOD) measures obtained throughout the dorsal raphe nucleus (DRN) in Mongolian gerbils at selected times during a 12:12 h light:dark cycle. Substantial diurnal variation occurred in 5-HT neuronal staining density, with lowest and highest IOD values occurring at the light/dark and dark/light transitions, respectively. The injection of pargyline and tryptophan increased 5-HT immunostaining comparable to the highest level observed in control animals. Transitions between light and dark periods appear to be major environmental events that influence 5-HT levels in the DRN.
The B fragment of cholera toxin (CTb) is a highly sensitive anterograde tracer for the labelling of retinal axons. It can reveal dense retinofugal projections to well-known retinorecipient nuclei along with sparse but distinct input to target areas that are not commonly recognized. Following a unilateral injection of CTb into the vitreous chamber of seven adult cats, we localized the toxin immunohistochemically in order to identify direct retinal projections in these animals. Consistent with previous findings, the strongest projections were observed in the superficial layers of the superior colliculus, the dorsal and ventral lateral geniculate nuclei, the pretectal nuclei, the accessory optic nuclei, and the suprachiasmatic nucleus of the hypothalamus. However, we also found labelled terminals in several other brain areas, including the zona incerta, the medial geniculate nucleus, the lateral posterior-pulvinar complex, the lateral habenular nucleus, and the anterior and lateral hypothalamic regions. The morphological characteristics of the retinal axon terminals in most of the identified novel target sites are described.
The serotonergic system has been implicated in the modulation of physiological processes including circadian rhythms, learning, memory, mood and food intake. In females, cessation of ovarian function produces deleterious changes in all of these processes and estrogen treatment often ameliorates these conditions. Estrogen may produce these effects by acting on the midbrain raphe, an estrogen-sensitive region that receives direct projections from sensory systems. Here we examined the ability of estradiol to modulate neuronal responses of neurons within raphe nuclei to photic stimulation. Ovariectomized rats treated with estradiol or cholesterol were killed 1 h after the normal onset of light (Zeitgeber time 0) or after a 2-h phase advance (Zeitgeber time 22). In a second study, estradiol-treated ovariectomized rats under constant dark conditions were exposed to light 2 h before the subjective onset of circadian time [(CT)22] and killed 1 h later (CT23). The brains from all animals were processed for Fos and/or serotonin (5-HT) immunocytochemistry. Comparisons showed that the phase shift increased Fos immunoreactivity in all dorsal raphe nucleus (DRN) regions. Although estradiol did not alter the overall number of Fos-positive nuclei, it significantly increased the number of Fos/5-HT double-labelled cells in the medial and lateral DRN. In contrast, neither a phase shift nor estradiol altered the number of Fos-immunoreactive cells or the proportion of Fos-positive 5-HT cells in the median raphe nucleus. Results reveal that the DRN 5-HT system responds to changes in the light : dark cycle and that these responses are modulated by estrogen.
In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG), was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine deaminase immunostaining was subsequently performed for the tuberomammillary nucleus (TMN) in order to investigate projections from the TMN to the two brainstem monoaminergic nuclei. Following rostral DR injections, the majority of retrogradely labeled cells were located in the dorsomedial and ventrolateral subdivisions of the TMN. At middle DR levels, midline injections resulted in labeling mainly in the ventrolateral subdivision, whereas lateral wing injections produced labeling mostly in ventral and caudal TMN subdivisions. When injections were made in the caudal DR, only a few cells were observed along the rostro-caudal extent of the TMN. On the other hand, following rostral LC injections, labeled neurons were observed mainly in ventrolateral and ventral subdivisions of TMN. For principal LC injections, labeled cells were observed mostly in ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at caudal pole of LC, only a few cells were located along the rostro-caudal extent of the TMN. In the second series of experiments, an iontophoretic injection of fluorogold (FG) into the DR was paired with a pressure injection of WG into the LC to investigate the collateral distribution of TMN axonal fibers to DR and LC. Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN subdivisions. The present study indicated that there exists a robust projection from the TMN to the DR or the LC and that some TMN neurons have axon collaterals projecting to both DR and LC. The TMN neurons with such axon collaterals might provide simultaneous, possibly more efficient, way of controlling the brainstem monoaminergic nuclei, thus influencing various sleep and arousal states of the animal.
In this study, we report the identification of a hitherto not reported direct retinal projection to midline and intralaminar thalamic nuclei in the marmoset brain. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-immunoreactive fibers and presumptive terminals were seen in the following thalamic midline nuclei: paraventricular, rhomboid, interanteromedial, and reuniens, and thalamic intralaminar nuclei: central medial, central lateral, central dorsal, and parafascicular. Studies employing sensitive tracers in other primate species are needed in order to verify the possible universality of these projections. Some of the possible functional correlates of the present data are briefly discussed. The present results may contribute to the elucidation of the anatomical substrate of the functionally demonstrated involvement of this midline/intralaminar thalamic nuclear complex in several domains that include arousal and awareness, besides specific cognitive, sensory, and motor functions.
A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. Following WG injections into rostral DR, WG-single-labeled cells were observed at the dorsal half of the LH as well as dorsomedial hypothalamic nucleus. The major input to the intermediate DR originates from the ventromedial portion of the LH, PeF, and the area dorsal to the PeF, whereas one to lateral wing DR derived from PeF as well as the ventrolateral portion of the LH. Following WG injections into caudal DR, WG-single-labeled cells were located at ventromedial LH and the ventrolateral portion of the posterior hypothalamus. Following WG injections into each DR subdivision, WG/orexin-double-labeled neurons were observed at LH, PeF, and the area dorsal to the PeF. Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.
Since 1892, anatomical studies have demonstrated that the retinas of mammals, including humans, receive input from the brain via axons emerging from the optic nerve. There are only a small number of these retinopetal axons, but their branches in the inner retina are very extensive. More recently, the neurons in the brain stem that give rise to these axons have been localized, and their neurotransmitters have been identified. One set of retinopetal axons arises from perikarya in the posterior hypothalamus and uses histamine, and the other arises from perikarya in the dorsal raphe and uses serotonin. These serotonergic and histaminergic neurons are not specialized to supply the retina; rather, they are a subset of the neurons that project via collaterals to many other targets in the central nervous system, as well. They are components of the ascending arousal system, firing most rapidly when the animal is awake and active. The contributions of these retinopetal axons to vision may be predicted from the known effects of serotonin and histamine on retinal neurons. There is also evidence suggesting that retinopetal axons play a role in the etiology of retinal diseases.
Retinal projections and visual thalamo-cortical connections were studied in the subterranean mole rat, belonging to the superspecies Spalax ehrenbergi, by anterograde and retrograde tracing techniques. Quantitative image analysis was used to estimate the relative density and distribution of retinal input to different primary visual nuclei. The visual system of Spalax presents a mosaic of both regressive and progressive morphological features. Following intraocular injections of horseradish peroxidase conjugates, the retina was found to project bilaterally to all visual structures described as receiving retinal afferents in non-fossorial rodents. Structures involved in form analysis and visually guided behaviors are reduced in size by more than 90%, receive a sparse retinal innervation, and are cytoarchitecturally poorly differentiated. The dorsal lateral geniculate nucleus, as defined by cyto- and myelo-architecture, cytochrome oxidase, and acetylcholinesterase distribution as well as by afferent and efferent connections, consists of a narrow sheet 3–5 neurons thick, in the dorsal thalamus. Connections with visual cortex are topographically organized but multiple cortical injections result in widespread and overlapping distributions of geniculate neurons, thus indicating that the cortical map of visual space is imprecise. The superficial layers of the superior colliculus are collapsed to a single layer, and the diffuse ipsilateral distribution of retinal afferents also suggests a lack of precise retinotopic relations. In the pretectum, both the olivary pretectal nucleus and the nucleus of the optic tract could be identified as receiving ipsilateral and contralateral retinal projections. The ventral lateral geniculate nucleus is also bilaterally innervated, but distinct subdivisions of this nucleus or the intergeniculate leaflet could not be distinguished. The retina sends a sparse projection to the dorsal and lateral terminal nuclei of the accessory optic system. The medial terminal nucleus is not present.
In contrast to the above, structures of the “non-image forming” visual pathway involved in photoperiodic perception are well developed in Spalax. The suprachiasmatic nucleus receives a bilateral projection from the retina and the absolute size, cytoarchitecture, density, and distribution of retinal afferents in Spalax are comparable with those of other rodents. A relatively hypertrophied retinal projection is observed in the bed nucleus of the stria terminalis. Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub-paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon. These results indicate that the apparently global morphological regression of the visual system conceals a selective expansion of structures related to functions of photoperiodic perception and photo-neuroendocrine regulation.
We suggest that the evolution of an atrophied eye and reduced visual system is an adaptively advantageous response to the unique subterranean environment. Factors favoring regression include mechanical aspects, metabolic constraints, and competition between sensory systems. The primary advantage of sensory atrophy is the metabolic economy gained by the reduction of visual structures which do not contribute significantly to the animal's fitness.
Bright artificial light has been found effective in reducing winter depressive symptoms of Seasonal Affective Disorder, although conclusions about the true magnitude of treatment effect and importance of time of day of light exposure have been limited by methodologic problems. Individual subjects' data from 14 research centers studying 332 patients over 5 years were analyzed with a pooled clustering technique. Overall, 2500-lux intensity light exposure for at least 2 hours daily for 1 week resulted in significantly more remissions--Hamilton Depression Rating Scale (HAM-D) score reduction of 50% or more to a level under 8--when administered in the early morning (53%) than in the evening (38%) or at midday (32%). All three times were significantly more effective than dim light controls (11%). Dual daily exposures (morning-plus-evening light) provided no benefit over morning light alone. In morning-evening crossovers, remission rates were 62% under morning light alone, compared with 28% under evening light alone, with a differential morning-evening response present in 59% of morning responders compared with 10% of evening responders (p less than 0.001). Remission rates with morning light were highest given low severity at baseline (HAM-D score of 10-16: 67% remission), as compared with moderate-to-severe cases (HAM-D score above 16: approximately 40% remission) where no morning-evening differences were found. Firmer conclusions await treatment studies with larger sample sizes and full assessment of atypical vegetative symptoms seen in winter depression but underrepresented in the Hamilton scale. Longer treatment course and greater light intensity may help clarify clinical response despite the impossibility of achieving a conventional blind placebo control.
We report an improved immunohistochemical protocol for revealing anterograde axonal transport of the subunit B of cholera toxin (CTB) which stains axons and terminals in great detail, so that single axons can be followed over long distances and their arbors reconstructed in their entirety. Our modifications enhance the quality of staining mainly by increasing the penetration of the primary antibody in the tissue. The protocol can be modified to allow combination in alternate sections with tetramethylbenzidine (TMB) histochemical staining of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Using the protocol, we tested the performance of CTB as an anterograde tracer under two experimental paradigms which render other anterograde tracers less sensitive or unreliable: (1) labeling the entire retinofugal projection to the brain after injections into the vitreal chamber of the eye, and (2) labeling developing projections in the cortex and thalamus of early postnatal mammals. Qualitative comparisons were made with other tracers (Phaseolus vulgaris leucoagglutinin, dextran rhodamine, biotinylated dextran, free WGA, or WGA-HRP) that were used to label these same projections. From these observations it is clear that CTB, visualized with our protocol, provides more sensitive anterograde labeling of retinofugal projections as well as of axonal connections in the neonatal forebrain.
TEMPORAL changes of serotonin (5-HT) content in the median (MRN) and dorsal (DRN) raphe nuclei were measured in rats kept under various lighting conditions. Serotonin content in the MRN and DRN under light-dark (LD) condition showed diurnal rhythmicity, with a peak during early light wphase and a trough during the dark phase. In constant dark (DD) condition, a single peak was observed and was out of phase to the 5-HT peak found under LD condition. Animals exposed to constant light (LL) after 2 days in DD showed marked increase in 5-HT after lights on. These results suggest that changes in 5-HT in the MRN and DRN are regulated by an endogenous pacemaker and by light.
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The effect of serotonin 5-HT2 receptor stimulation on long-term potentiation (LTP) in the primary visual cortex was investigated by using rat brain slices in vitro. Field potentials evoked by stimulation of layer IV were recorded in layer II/III. The 5-HT2 receptor agonist 1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane (DOI) did not affect baseline synaptic potentials evoked by single-pulse test stimulation, but significantly inhibited the induction of LTP in a concentration-dependent manner (0.1–10 μm). The LTP-inhibiting effect of DOI (10 μm) was blocked by the 5-HT2,7 receptor antagonist ritanserin (10 μm), but not by the 5-HT1A receptor antagonist NAN-190 (10 μm) nor by the 5-HT3,4 receptor antagonist MDL72222 (10 μm). The inhibitory effect of DOI was also blocked by the phospholipase C inhibitor U73122, but not by its inactive analogue U73343. These results suggest that visual cortex LTP is inhibited by activation of the 5-HT2 receptor–phospholipase C system. In addition, the LTP-inhibiting effect of DOI was abolished by the presence of the GABAA receptor antagonist bicuculline (10 μm), suggesting that 5-HT2 receptor-mediated inhibition of visual cortex LTP is dependent on GABAergic inhibition.
Previous reports from this laboratory and elsewhere have provided evidence that the locus coeruleus (LC) and dorsal raphe (DR) nuclei are topographically organized with respect to their efferent targets. Whereas most of these previous studies have focused on relationships between these monoamine-containing brainstem nuclei and cerebral cortex, basal ganglia, and limbic structures, they have not systematically examined the distribution of LC and DR cells that project to multiple structures with common sensory or motor functions. The goal of the present study was to characterize and compare the distributions of LC and DR cells which project to different visual areas of the rat central nervous system. Long-Evans hooded rats received unilateral pressure injections of the retrograde tracer wheat germ agglutinin-horseradish peroxidase in either the dorsal lateral geniculate, ventral lateral geniculate, or lateral posterior nucleus of thalamus; superior colliculus, cortical area 17, cortical area 18a/b cerebellar vermis (lobules VI and VII); or paraflocculus. Transverse sections through the midbrain and pons were examined by light microscopy after performing routine tetramethyl benzidine histochemical procedures. For all cases studied, retrogradely labeled cells were observed throughout the rostrocaudal extent of the LC and DR; however, labeling patterns which were distinctive for different injection sites were noted in each of these brainstem nuclei. The major conclusion drawn from this work is that subsets of LC and DR cells which project to different target structures within the rat visual system are found in overlapping but not necessarily coextensive zones within these nuclei. These studies provide further evidence of a rough topographic ordering within both the LC and DR nuclei, as well as support a new hypothesis that the outputs from each of these nuclei are organized with respect to the sensory related functions of their efferent targets. © 1993 Wiley-Liss, Inc.
The present study was conducted to examine the spatial organization of dorsal (DR) and median (MR) raphe neurons that project to rostrocaudally aligned areas of the rat cerebral cortex. An additional goal was to determine if individual DR cells that send efferents to forelimb sensorimotor or visual regions of the neocortex also send axon collaterals to forelimb (crus II) or visual (paraflocculus) areas of the cerebellum. Long-Evans hooded rats received unilateral pressure injections of horseradish peroxidase (HRP) in either motor n = 4) or sensorimotor (n = 5) or visual (n = 4) cortex to determine the intranuclear location of DR and MR neurons that project to specific neocortical regions. Coronal sections (40-100 μm) through the pons and midbrain were examined by light microscopy after the tetramethyl benzidine reaction and neutral red counterstaining were carried out. The locations of retrogradely labeled cells were recorded relative to a threedimensional biological coordinate system maintained by a computer linked to the light microscope. For double labeling studies, unilateral injections of fast blue and nuclear yellow were made in paired motor (sensorimotor cortex and crus II of the lateral cerebellum) or visual (cortical area 17 and paraflocculus) areas of the CNS. Coronal tissue sections (35 μm) were collected on coverslips and examined on a Leitz fluorescence microscope (wavelength = 365 nm). DR neurons labeled from cerebrocortical injections of HRP were concentrated in the rostral two-thirds of the nucleus. HRP-filled neurons were distributed such that individual groups of neurons projecting to motor, sensorimotor, or visual cortex were aligned in a partially overlapping, rostral to caudal array. In the dorsoventral dimension, retrogradely labeled cells were clustered in three distinct groupings such that neurons projecting to the motor, sensorimotor, and visual areas were concentrated in dorsal, intermediate, and ventral portions of the DR nucleus, respectively. For all cases, the majority of HRP-filled cells were positioned along the midline or displaced to the side of the nucleus that was ipsilateral to the cortical injection site. A small number of retrogradely labeled neurons were observed in the MR following injections in the motor cortex. Computer-assisted reconstruction of th z neuroanatomical data facilitated the visualization of spatial relationships between groups of DR neocortical projection neurons. Twenty to 30% of the cells labeled in the DR after paired injections of fast blue and nuclear yellow in sensorimotor or visual areas of the neocortex and cerebellum were doubled labeled indicating that individual DR neurons can send axon collaterals to functionally analogous regions of the CNS. Overall, the results indicate that, within the DR, a topographic ordering exists with respect to rostrocaudally aligned terminal fields in the neocortex. In addition, a portion of the DR cerebrocortical projection neurons also send axon collaterals to specific regions of the cerebellar cortex. The intranuclear organization observed in this study suggests that neuronal activity in distinct regions of the DR nucleus may independently influence discrete populations of cerebrocortical cells. Furthermore, the possibility must now be considered that a substantial number of single DR neurons provide a common input via axon collerals to portions of the neocortical and cerebellar circuitry that receive afferent information related to the same sensory or motor function.
Immunocytochemistry revealed in the retina of the Mongolian gerbil three immunologically distinct photoreceptor cell types. Rods comprising about 87% of the total receptor population were selectively recognized by an antirhodopsin serum (AO). The most abundant cone type (11-13% of photoreceptors) was labeled by the monoclonal antibody COS-1, specific in mammals to the middle-to-long-wave sensitive cone visual pigments. A minor cone population (2.5-5% of the cones) reacted with the monoclonal antibody OS-2, shown earlier to bind to the blue cones in mammalian species. Color substitution experiments revealed on the ERG level a color discrimination capability which must be attributed to the cooperative activity of green-sensitive (COS-1 positive) and blue-sensitive (OS-2 positive) cones. We conclude that the Mongolian gerbil has a well developed cone system, and that it may possess dichromatic green-blue color vision.
Ascending projections from the dorsal raphe nucleus (DR) were examined in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from the DR ascended through the forebrain within the medial forebrain bundle. DR fibers were found to terminate heavily in several subcortical as well as cortical sites.
The following subcortical nuclei receive dense projections from the DR: ventral regions of the midbrain central gray including the ‘supraoculomotor central gray’ region, the ventral tegmental area, the substantia nigra-pars compacta, midline and intralaminar nuclei of the thalamus including the posterior paraventricular, the parafascicular, reuniens, rhomboid, intermediodorsal/mediodorsal, and central medial thalamic nuclei, the central, lateral and basolateral nuclei of the amygdala, posteromedial regions of the striatum, the bed nucleus of the stria terminalis, the lateral septal nucleus, the lateral preoptic area, the substantia innominata, the magnocellular preoptic nucleus, the endopiriform nucleus, and the ventral pallidum. The following subcortical nuclei receive moderately dense projections from the DR: the median raphe nucleus, the midbrain reticular formation, the cuneiform/pedunculopontine tegmental area, the retrorubral nucleus, the supramammillary nucleus, the lateral hypothalamus, the paracentral and central lateral intralaminar nuclei of the thalamus, the globus pallidus, the medial preoptic area, the vertical and horizontal limbs of the diagonal band nuclei, the claustrum, the nucleus accumbens, and the olfactory tubercle.
The piriform, insular and frontal cortices receive dense projections from the DR; the occipital, entorhinal, perirhinal, frontal orbital, anterior cingulate, and infralimbic cortices, as well as the hippocampal formation, receive moderately dense projections from the DR.
Some notable differences were observed in projections from the caudal DR and the rostral DR. For example, the hippocampal formation receives moderately dense projections from the caudal DR and essentially none from the rostral DR. On the other hand, virtually all neocortical regions receive significantly denser projections from the rostral than from the caudal DR.
The present results demonstrate that dorsal raphe fibers project significantly throughout widespread regions of the midbrain and forebrain.
Although Syrian hamsters and Mongolian gerbils are closely related, they have quite different patterns of retinal ganglion cell distribution and different patterns of retinal growth that produce their distributions. We have examined the morphology and distribution of catecholaminergic (CA) neurones in adult and developing retinae of these species in order to gain a more general understanding of the mechanisms producing cellular topographies in the retina. CA neurones were identified with an antibody to tyrosine hydroxylase (TH), the rate limiting enzyme in the production of catecholamines.
In adult retinae of both hamsters and gerbils, most CA somata were located in the inner part of the inner nuclear layer (INL) and CA dendrites spread in a outer stratum of the inner plexiform layer (IPL). Their somata varied with retinal position, being largest in temporal and smallest in central retina. In hamsters, but not gerbils, a small number of CA interplexiform cells was also observed. In development, CA somata of hamster retinae were observed first in the middle and /or scleral regions of the cytoblast layer (CBL) at P (postnatal day) 8. By P12, CA somata were commonly located in the inner part of the INL and their dendrites spread into the outer region of the IPL. In developing gerbil retinae, CA somata were first observed at P6 in the middle of the CBL. Over subsequent days, they migrated into the inner part of the INL and spread their dendrites into the outer strata of the IPL.
In both hamsters and gerbils, CA cells were initially concentrated in the superior temporal margin of the retina. In hamsters, this supero‐temporal concentration persisted until adulthood, whereas in adult gerbils, the greatest density of CA cells was found just superior to the visual streak. These distributions were distinct from those of the ganglion cells in adult and developing retinae of each species. We discuss the role of maturational expression of TH, cell death, and retinal growth in the generation of the distinct distribution of the CA cells.
In Part a of the study, the retinal inputs to the hypothalamus, anterior thalamus and basal forebrain of Syrian hamsters were studied using intraocular injections of horseradish peroxidase conjugated to cholera toxin (CT-HRP). In the hypothalamus, the heaviest retinal input was to the suprachiasmatic nucleus (SCN), however, many labeled fibers coursed through the SCN to reach more caudal, periventricular and lateral sites including the anterior and lateral hypothalamus, the paraventricular nucleus (PVN), the subparaventricular zone, the ventromedial nucleus and the pars compacta of the dorsomedial nucleus. Some of these fibers continued dorsally into the zona incerta (ZI). Other fibers emerged from the lateral optic chiasm and traveled either rostro-medially to end in the preoptic area (POA) or further laterally to reach the supraoptic nucleus. A subset of fibers extended laterally from the chiasm to form a well-defined tract which provided input to the pyriform cortex. The extrageniculate retinal input to the thalamus was to the anterior thalamic area (AT) via the stria terminalis. In Part b, injections of rhodamine-labeled latex microspheres were made in three brain areas that contained labeled fibers after intraocular injections of CT-HRP. Injections in the AT, PVN/ZI area and POA consistently produced a small number of labeled retinal ganglion cells, whereas control injections did not. Taken together, these results indicate that many regions of the brain involved in the control of reproductive and regulatory functions receive photic informations via direct retinal inputs. These retinal inputs may play a role in the photoperiodic modulation of physiology and behavior.
Binding of paroxetine to blood platelet membranes was studied longitudinally in 20 healthy volunteers (11 men and 9 women) in order to determine seasonal and gender variations. Blood samples were obtained in September, December, March, and June, and repeated in September. A significant seasonal variation in the maximal number of binding sites (Bmax) was found. Men were found to have significantly lower (Bmax) values than women. Although the pattern of seasonal variation was not identical in men and women, no significant differences were detected. The affinity constant (KD) of paroxetine binding showed a significant seasonal variation. Men were found to have a significantly higher KD (lower affinity) than women. The pattern of seasonal variation was identical in men and women. These data support the evidence indicating a substantial seasonal effect on the serotonergic system, and show that in paroxetine binding studies, groups of subjects should be matched for season and gender.
Single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN), heart rate (HR), and arterial blood pressure were recorded in freely moving cats during spontaneous behavior and in response to systemic administration of vasoactive drugs. The activity of serotonergic neurons varied in association with behavioral arousal but was unrelated to spontaneous fluctuations in HR and blood pressure. Bolus administration of phenylephrine hydrochloride and sodium nitroprusside (15-20 micrograms/kg iv) produced a rapid transient increase (35 mmHg) and decrease (49 mmHg), respectively, in mean arterial pressure (MAP). Infusion of phenylephrine and sodium nitroprusside (100 micrograms/ml) produced sustained hypertension (avg MAP 166 mmHg) and hypotension (avg MAP 49 mmHg), respectively. The activity of serotonergic neurons was not significantly altered in response to phenylephrine or sodium nitroprusside administration. Furthermore, no significant changes in unit activity were observed after hydralazine administration (1 mg/kg iv) despite prolonged reflex activation of sympathetic outflow. Thus the activity of DRN serotonergic neurons was unrelated to transient alterations in blood pressure and baroreceptor activity. These results suggest that changes in the activity of serotonergic DRN neurons are not involved in physiological mechanisms underlying reflex alterations in sympathetic (and parasympathetic) outflow invoked by hypertension and hypotension.
Electrophysiological studies were conducted on chloral hydrate-anesthetized rats to determine if the dorsal raphe nucleus (DR) exerts an inhibitory influence upon the dorsal lateral geniculate nucleus (dLGN), and if this inhibition is mediated by the release of serotonin (5-HT). Conditioning stimuli presented to the DR 100-400 ms before an optic tract (OT) shock significantly lowered the amplitude of OT shock-elicited, postsynaptic, field potentials of less than 3 ms latency. Rare, long-latency, field potentials (greater than 5 ms) were diminished in amplitude when preconditioning intervals were less than 15 ms. Six days after intracerebral injection of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (8 micrograms), into the dLGN, significant reductions were observed in 5-HT and 5-hydroxyindole acetic acid in the dLGN. Field potentials recorded on the sixth day in indoleamine-depleted dLGN were significantly less inhibited by DR preconditioning. Intracerebral injections of a control solution neither altered monoamine levels nor the degree of inhibition by DR preconditioning. These data provide further evidence that inhibition of dLGN by DR is mediated by release of 5-HT.
We have studied the serotonergic (5-HT) projection to the cat superior colliculus (SC) using serotonin antibody immunocytochemistry and retrograde transport of peroxidase-conjugated wheatgerm agglutinin (WGA-HRP). In 3 experiments, the two labels were combined in order to double label cells with both anti-5-HT and WGA-HRP. In the remaining experiments, the two labels were examined separately. Serotonin-like immunoreactive fibers were found throughout all layers of SC, but were most densely distributed within the zonal and upper superficial gray layers. Most 5-HT fibers were thin and had characteristic varicosities and terminal swellings. At the EM level, immunoreactive terminals and varicosities were found to contain small agranular vesicles and occasionally large granular vesicles (LGVs). Conventional synaptic densities were only rarely observed. Injections of WGA-HRP into SC resulted in labeling of neurons throughout the dorsal raphe nucleus and surrounding ventrolateral periaqueductal gray. Only a few cells were found in the raphe medianus and raphe pontis and none within the raphe magnus or other medullary raphe nuclei. Cells in the dorsal raphe giving rise to the SC projection varied in shape, size, and morphology and must represent more than one cell type. The morphology of these cells was indistinguishable from that of cells in the dorsal raphe which were double labeled by anti-5-HT and WGA-HRP. We conclude that the 5-HT innervation of the superior colliculus varies in density in different laminae, arises from several different cell types, and originates primarily from the dorsal raphe nucleus with minor projections from raphe medianus and raphe pontis.
Retinal projections were studied in species from 8 orders of mammals using anterograde tracing techniques. The olfactory tubercle of basal telencephalon receives a projection from the retina in all animals. In all species the course of labelled fibers is similar and the terminal distribution of label along the internal border of the granular cell layer is restricted to the mediocaudal region of the tubercle. These shared characteristics suggest that this pathway is a typical mammalian feature, possibly providing for convergence of visual and chemosensory information in telencephalon.
The effect of stimulating the dorsal raphe nucleus (DRN) on the activity of single relay neurons in the dorsal lateral geniculate nucleus (LGNd) was studied in rats anesthetized with urethane. The position of stimulating electrodes was confirmed on histological sections processed with NADPH-diaphorase histochemistry which could delineate the DRN clearly. During repetitive stimulation of the DRN at 200 Hz for several to 10 seconds no consistent change in firing was observed, but between several and several tens of seconds after the cessation of stimulation spontaneous firing of LGNd neurons was suppressed. In many cases the suppression proceeded concomitantly with augmentation of slow waves in the cortical EEG. The suppression was mimicked by ionophoresis of serotonin, and antagonized by a serotonergic antagonist, methysergide. In addition, in animals in which DRN stimulation became ineffective after it was evoked many times, the suppression could be restored by intraperitoneal administration of a serotonin precursor, 5-hydroxytryptophan. Compilation of peristimulus time histograms revealed that a brief DRN stimulation (5 shocks at 1000 Hz) could also elicit the suppression lasting from 60 to 100 ms or longer after the shocks. These results suggest that serotonin released from terminals of DRN neurons exerts long-latency and long-lasting inhibition of LGNd relay neurons. Along with brainstem noradrenergic and cholinergic systems, the serotonergic projection from the DRN acts to control excitation levels of the forebrain.
The response of noradrenergic (NE), serotonergic (5-HT), and dopaminergic (DA), neurons to repeated presentations (once/2 s for 64 trials) of phasic auditory (click) and visual (flash) stimuli was examined in freely moving cats. All 3 groups of neurons displayed similar response latencies and somewhat similar durations of excitation to both stimulus modalities. 5-HT neurons in the mesencephalic raphe nuclei showed no decrease in responsiveness across trials to either of the stimuli. DA neurons in the substantia nigra displayed no decrease in responsiveness across trials to the auditory stimulus, but did display an approximately 50% decrease in response to the visual stimulus. NE neurons in the locus coeruleus showed an approximately 50% decrease in responsiveness to both the auditory and visual stimuli. These data are consistent with previous studies showing that the response of many neurons in the brainstem reticular formation habituates to the repetitive presentation of sensory stimuli. They also show that the response of reticular formation neurons are heterogeneous and that they can be subdivided on the basis of their neurochemical identity. Finally, these data provide support for the involvement of NE neurons, and to a lesser extent DA neurons, in various forms of behavioral plasticity.
Spontaneous activity of the nucleus raphe dorsalis (NRD) neurons during the sleep-waking cycle and effects of sensory stimuli upon NRD neurons were studied in cats. Seventy-one neurons recorded within the NRD were classified into two groups with the use of the coefficient of variation of firing intervals during waking (W): 41 regularly firing (clock-like) and 30 irregularly firing (non-clock-like) neurons. The majority of clock-like and one-third of non-clock-like neurons showed a decrease in their firing rate during slow-wave sleep (SWS) compared with W. All neurons of both types displayed their lowest level of activity during paradoxical sleep. During the late phase of SWS, many clock-like neurons reduced their firing prior to the occurrence of pontogeniculo-occipital waves, whereas non-clock-like neurons did not show such a specific property. Clock-like neurons were totally unresponsive to nociceptive and non-nociceptive somesthetic stimuli, while about half of the non-clock-like neurons were driven by these stimuli. Half of the clock-like and one-third of the non-clock-like neurons were driven by click stimulation, and the majority of them showed an excitatory response. Some of the clock-like and non-clock-like neurons exhibited inhibitory and excitatory response to flash stimulation, respectively. The results of this experiment show that two types of neurons do exist in the NRD and suggest that they play a functionally different role in the brain.
A cross-over comparison study of exposure, in the evenings only, to bright versus dim light was carried out on nine female patients with seasonal affective disorder. A significant antidepressant effect of the bright lights was shown. No consistent observable effects were produced by the dim lights. These results support earlier studies demonstrating the efficacy of bright light given morning and evening. The antidepressant effect of light is not mediated by sleep deprivation, and the early morning hours are not crucial for a response.
The effects of phasic auditory or visual stimuli upon the single unit activity of serotonergic neurons within the dorsal raphe nucleus (DRN) were studied in freely moving cats. The predominant response to auditory stimulation (86% of the cells) was excitation, with a mean latency of 40 +/- 3 ms (S.E.M.) and a mean duration of 64 +/- 4 ms. This was typically followed by a longer period (206 +/- 32 ms) with unit activity below the baseline level. This did not appear to be a stimulus-induced inhibition of unit activity, however, since its duration closely corresponded to the normal interspike interval for that particular neuron. The response to repetitive auditory stimulation showed no evidence of habituation and was even present during sleep. A similar response, although generally of lesser magnitude, was evoked by a phasic visual stimulation in 64% of the cells tested. The mean latency for the response to visual stimulation was 53 +/- 4 ms, the mean duration of excitation was 76 +/- 7 ms, and the mean duration of the subsequent suppressed period was 239 +/- 37 ms. The response to the visual stimulus also showed no evidence of habituation. These data indicate that serotonergic neurons of the DRN are driven, with similar temporal characteristics, by stimuli in two different sensory modalities. We hypothesize that these similar effects are attributable to a common excitatory input.
Retinal projections to the basal forebrain in male Syrian hamsters were examined at the ultrastructural level following bilateral intraocular injections of horseradish peroxidase conjugated to either cholera toxin (CT-HRP) or wheat germ agglutinin (WGA-HRP). Light level microscopic analysis confirmed retinal projections along basal telencephalon, and examination on the electron microscope of individual fibers from the peri-amygdaloid area revealed en passant synaptic profiles. Sections from animals treated with WGA-HRP showed evidence of transsynaptic communication in the form of labeled dendrites in the peri-amygdaloid area. Taken together, these data show that the retina communicates directly with the periamygdaloid area, where photic and chemosensory information may be integrated to modulate reproductive behavior.
For direct measurement of the extracellular concentration of serotonin (5-HT) in the dorsal raphe nucleus (DRN) over the sleep-wake cycle we used the technique of in vivo microdialysis in six freely moving, naturally sleeping cats whose behavioral state was polygraphically determined. Perfusate samples from microdialysis probes histologically localized to the DRN showed the following significantly different levels of extracellular 5-HT, with the numbers in parentheses indicating successively the mean value in fmol/5 microliters perfusate sample, the % level relative to waking, and the sample n: waking (4.02, 100%, n = 38) > slow wave sleep (2.02, 50%, n = 30) > REM sleep (1.61, 38%, n = 17). These data, to our knowledge the first direct DRN 5-HT measurements during behavioral state changes, directly parallel the levels of serotonergic neuronal action potential activity and suggest that DRN extracellular 5-HT is determined by this action potential activity through synaptic release by recurrent axonal collaterals in the DRN.
Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was recorded in free-moving cats in response to i.v. administration of 5-hydroxytryptamine (5-HT)1A agonist and antagonist drugs. The 5-HT1A agonist drugs 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), ipsapirone, buspirone and 5-methoxy-N,N-dimethyltryptamine produced a rapid, dose-dependent inhibition of neuronal activity. 8-OH-DPAT (ED50 = 1.5 micrograms/kg) was approximately 45 times more potent than ipsapirone, buspirone or 5-methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 micrograms/kg) in producing inhibition, and all drugs were more effective when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT1A autoreceptor antagonist spiperone (0.25 and 1 mg/kg) produced a rapid, dose-dependent increase in the firing rate, suggesting that under physiological conditions serotonergic neurons are controlled by tonic feedback inhibition. This effect was evident during wakefulness (a period of relatively high neuronal activity), but not during sleep (a period of relatively low neuronal activity). Spiperone also blocked the inhibitory action of 8-OH-DPAT in a dose- and time-dependent manner. There was a strong positive correlation between the magnitude of spiperone-induced neuronal activation and blockade of 8-OH-DPAT-induced neuronal suppression. These effects of spiperone cannot be attributed to its dopaminergic D2 or serotonergic 5-HT2 antagonist properties, because administration of haloperidol and ritanserin produced no increase in neuronal activity and did not block the action of 8-OH-DPAT. These results confirm the marked sensitivity of serotonergic dorsal raphe nucleus neurons to selective 5-HT1A agonist compounds in unanesthetized animals and suggest that 5-HT1A somatodendritic autoreceptors exert a tonic inhibitory influence on the firing rate of these neurons during periods of behavioral activation, but not during periods of behavioral quiescence.
1. Radioligand binding with [125I]-cyanopindolol in the presence of isoproterenol was used to define the distribution of 5-HT1B receptors in the superior colliculus (SC) of adult hamsters. There was a high density of these receptors in the stratum griseum superficiale (SGS), and they were much less dense in other SC laminae. Enucleation of one eye produced a marked reduction in the density of these receptors in the contralateral SGS, suggesting that they are located primarily on retinotectal axon terminals. 2. Intracellular recording techniques were used to evaluate the effects of serotonin (5-HT) on the excitatory postsynaptic potentials (EPSPs) evoked in SC cells of adult hamsters by stimulation of the optic tract (OT) in vitro. Application of 5-HT produced a reduction of > or = 50% in OT-evoked EPSPs in 79% of the 67 cells tested. The average EPSP amplitude was 7.8 +/- 2.1 (SD) mV under control conditions and 2.7 +/- 1.9 mV in the presence of 5-HT (P < 0.01). For most of these neurons, application of 5-HT had little effect on their membrane potential or input resistance. The average percent change in membrane potential for cells tested with 5-HT was 0.5 +/- 6.0% and the average percent change in input resistance was 0.6 +/- 22.9%. 3. For four of six cells tested, application of 5-HT had no significant effects on the responses evoked by application of glutamate, either under normal bathing conditions or when the medium included low Ca2+ and high Mg2+. 4. Pharmacologic experiments indicated that the effects of 5-HT on retinotectal transmission were mimicked by the 5-HT1B agonists 1-[3-(trifluoromethyl)phenyl]-piperazine and 7-trifluoromethyl-4(4-methyl-1-piperazinyl) [1,2-a]-quinoxaline maleate and antagonized by the 5-HT1A/1B antagonists (-)-pindolol and methiothepin. The effects of 5-HT on the OT-evoked EPSP were not antagonized by either spiperone, ketanserin, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine HBr, or [1-H-3 alpha-5 alpha-tropan-3-yl]-3,5-dichlorobenzoate. 5. Both the anatomic and physiological results are consistent with the conclusion that 5-HT presynaptically inhibits retinotectal transmission and that this effect is mediated by the 5-HT1B receptor.
A direct projection from the retina to the dorsal raphe nucleus at the pontomesencephalic junction was demonstrated with both antero- and retrograde tracing techniques in the rat. Following intravitreous injections of choleratoxin subunit B (CTB), horseradish peroxidase (HRP) and CTB-conjugated HRP, varicose fibers were labeled in the lateral region of the dorsal raphe nucleus, predominantly contralateral to the injection. Many of these labeled fibers were intermingled with serotonin-immunoreactive neurons, but some fibers were also found further laterally, beyond the boundary of dorsal raphe nucleus but within the periaqueductal gray. Following injections of the retrograde tracers Fluoro-Gold and CTB into the dorsal raphe nucleus and adjacent periaqueductal gray (without contamination of previously known targets of retinal projections), a small population of ganglion cells was labeled in the retina. These data provide evidence for the existence of a direct retinal projection to the lateral region of the dorsal raphe nucleus and the adjacent mesopontine periaqueductal gray in the rat. This projection may have a role in sensorimotor coordination and the regulation of circadian rhythm as well as sleep and wakefulness.
The retinal projection to the basal telencephalon was studied in eight species of primates from the suborders Strepsirhini and Haplorhini, including one anthropoid primate, the gibbon. Animals received an intraocular injection of tritiated amino acids and the distribution of retinal fibers and terminals was demonstrated by autoradiographic techniques in horizontal and coronal sections. In all species a discrete group of labeled retinal fibers is observed to branch off from the dorsolateral aspect of the optic tract at the level of the suprachiasmatic nucleus. These fibers, destined to the basal telencephalon, are topographically distinct from the retinal fibers which innervate the suprachiasmatic nucleus and medial hypothalamic regions. The fibers of the retinotelencephalic tract course dorsally above the supraoptic nucleus through the lateral hypothalamic area and then proceed further rostrally and laterally below the diagonal band of Broca towards the olfactory tubercle. Within the olfactory tubercle, terminal distribution of label is observed in the mediocaudal region along the granular cell layer II. In the macaque this cellular layer shows a characteristic thickening in the region of retinal terminals which is evident in both coronal and horizontal section. In some species this labeled region is seen within the superficial bulge of the tubercle on the ventral aspect of basal telencephalon. In all primates the retinal projection to olfactory tubercle is bilateral. In prosimians label is predominantly contralateral to the injected eye, in New World monkeys label is equally distributed on both sides of the brain and in Old World monkeys label is mainly found ipsilaterally. Retinal fibers were also seen in the periamygdaloid region but never extended as far as piriform cortex. These results, in addition to previous studies in other mammalian orders, confirm that the basal telencephalon, and in particular the olfactory tubercle, constitutes a region of visual and olfactory convergence. This sensory integration may be related to photic and chemosensory modulation of reproductive physiology and behavior.
Possible pathways from the retina to the suprachiasmatic nucleus (SCN) relaying in the dorsal raphe nucleus (DRN) were investigated in rats using combined anterograde and retrograde tracing with immunohistochemistry. After injection of wheat germ agglutinin-conjugated horseradish peroxidase-colloidal gold complex into the SCN, many neurons were retrogradely labeled in the middle levels of the DRN. Approximately one half of these neurons contained serotonin. After injection of cholera toxin B subunit into the eyes, a few anterogradely labeled afferent fibers were detected in the rostral DRN, however, not in contact with retrogradely labeled neurons. Our findings provide direct evidence that serotonergic projections to the rat SCN stem from the DRN nuclei. They also suggest that retina-raphe-SCN projections, a presumed third visual input to the mammalian circadian pacemaker, may include further neuronal connections or brain sites.
The projection from the retina to the habenular complex was studied using fluorescent retrograde tracers in the albino rat (Wistar, Japan Clea). Following separate unilateral injections of Fluoro-Gold (FG), Fluoro-Ruby (FR), or 4-acetamido,4- isothiocyanostilbene-2,2'-disulfonic acid (SITS) into the lateral habenular nucleus (LHB), a small population of ganglion cells was labeled sporadically, predominantly those in the nasal retina contralateral to each injection site. Most of them were small cells, ranging from 9 to 16 mu m in diameter, roughly corresponding to the type III ganglion cell in the rat retina. Additionally, all of the structures previously described as regions projecting to the LHB were confirmed. Upon re-examination of previous brain sections of albino rats which had undergone monocular enucleation, degenerating retinal nerve axons and/or their terminals, stained by a modified selective silver impregnation method, were observed in the well-documented end regions of retinal afferents as well as the LHB. The degenerating retino-habenular nerve terminals were distributed sparsely and restricted mainly to the caudal part of the LHB contralateral to the side of ocular enucleation. The present experimental data provide evidence for the existence of a non-image forming retino-habenular pathway in the albino rat. We suggest that, besides serving as a point of convergence for some of the major conduction channels of the limbic and striatal systems, the LHB may play more general integrative roles, including participation in the integration of visual information.
A dense serotonin (5-HT)-containing projection to the superficial layers of the superior colliculus (SC) has been demonstrated in diverse mammalian species, but how 5-HT may affect visual signals within these laminae is largely unknown. This study undertook to investigate the distribution of 2 types of 5-HT receptors in the SC and to ascertain their physiological effects on transmission of visual signals to the SC from the retinotectal and corticotectual pathways. Autoradiography of tissue sections exposed to [3H]-8-OH-DPAT (8-hydroxy-dipropylaminotetraline) or to [125I]cyanopindolol plus isoproterenol showed that 5-HT1A and 5-HT1B receptors, respectively, were present in the superficial SC layers. In unilaterally enucleated animals, binding of ligand to 5-HT1B receptors was greatly reduced on the deafferented (contralateral) side, which is consistent with the possibility that these receptors are located on preterminal axons. Binding to 5-HT1A receptors was unaltered by enucleation. In recordings of superficial layer neurons from SC slices, application of 5-HT during blockade of 5-HT1A receptors with spiperone reduced the amplitude of EPSPs evoked by stimulation of the optic tract. The 5-HT concentration for a 50% reduction in EPSP amplitude was 6 microM. Under these conditions, there were no significant alterations in either membrane potential or input resistance concurrent with 5-HT mediated reduction in EPSPs. During extracellular in vivo recordings, 5-HT, applied by iontophoresis or micropressure or by endogenous release produced by electrical stimulation of the dorsal raphé nucleus, strongly suppressed visual activity in SC neurons. The effectiveness of 5-HT application was significantly stronger on responses evoked by electrical stimulation of the optic chiasm (an average response decrement of 92.2%) than on these evoked in the same neurons by stimulation of visual cortex (an average response reduction of 32.3%). These results support the following conclusions. The 5-HT1B receptors are located preferentially on optic axon terminals and exert presynaptic inhibition of retinotectal inputs. Secondly, 5-HT1A receptors probably have a postsynaptic localization and may affect activity of SC neurons irrespective of the source of input. The combined effect of 5-HT at both subtypes would bias SC visual activity toward information received from the corticotectal pathway.
The objective of the present study was to identify the retinal ganglion cells projecting to the lateral hypothalamic area of the rat. The retinohypothalamic tract has been divided into a medial and a lateral component on anatomical and developmental grounds. The medial component projects to the suprachiasmatic nucleus and adjacent structures such as the anterior hypothalamic and retrochiasmatic areas. The lateral component terminates in the lateral hypothalamic are dorsal to the supraoptic nucleus. Injections of the retrograde tracer FluoroGold were made into the retinorecipient region of the lateral hypothalamic area and retinal whole mounts were immunohistochemically processed for retrogradely labeled retinal ganglion cells. With FluoroGold injections confined to the lateral hypothalamic area, retrogradely labeled retinal ganglion cells are located almost exclusively in the superior temporal quadrant of the retina. Their size and morphology indicates that they are a homogeneous subset of type III cells, but a definitive classification would require a more complete fill of dendritic arbors than is available in our retrograde material. In contrast, injections involving fibers of passage in the optic tract, or centered in the medial terminal nucleus of the accessory optic system, label cells distributed across the entire retinal surface. Unlike the retinal ganglion cells projecting to the suprachiasmatic nucleus [Moore et al., J. Comp. Neurol., 352 (1995) 351-366], the cells labeled after restricted lateral hypothalamic injections are not distributed evenly across the retinal surface. The difference in location of the retinal ganglion cells projecting to the lateral hypothalamic area supports the view that this retinohypothalamic projection is anatomically and functionally distinct from the projection to the suprachiasmatic nucleus and adjacent medial hypothalamus.
We investigated the effect of 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on the induction of long-term potentiation in rat visual cortex slices. Perfusion of 8-OH-DPAT (0.1-10 microM) did not affect layer II/III field potentials evoked by test stimulation of layer IV, but significantly reduced long-term potentiation induced by tetanic stimulation. The inhibitory effect of 8-OH-DPAT was blocked by the 5-HT1A receptor antagonist, pindolol (10 microM), but not by the 5-HT2,7 receptor antagonist, ritanserin (100 microM), nor by the 5-HT3,4 receptor antagonist, MDL72222 (100 microM). These results suggest that the rat visual cortex long-term potentiation is inhibited by 5-HT1A receptor stimulation.
The neural connections and neurotransmitter content of the suprachiasmatic nucleus and intergeniculate leaflet have been characterized thoroughly in only a few mammalian species, primarily nocturnal rodents. Few data are available about the neural circadian timing system in diurnal mammals, particularly those for which the formal characteristics of circadian rhythms have been investigated. This paper describes the circadian timing system in the diurnal rodent Octodon degus, a species that manifests robust circadian responses to photic and non-photic (social) zeitgebers. Specifically, this report details: (i) the distribution of six neurotransmitters commonly found in the suprachiasmatic nucleus and intergeniculate leaflet; (ii) the retinohypothalamic tract; (iii) the geniculohypothalamic tract; and (iv) retinogeniculate projections in O. degus. Using immunocytochemistry, neuropeptide Y-immunoreactive, serotonin-immunoreactive and [Met]enkephalin-immunoreactive fibers and terminals were detected in and around the suprachiasmatic nucleus; vasopressin-immunoreactive cell bodies were found in the dorsomedial and ventral suprachiasmatic nucleus; vasoactive intestinal polypeptide-immunoreactive cell bodies were located in the ventral suprachiasmatic nucleus; [Met]enkephalin-immunoreactive cells were located sparsely throughout the suprachiasmatic nucleus; and substance P-immunoreactive fibers and terminals were detected in the rostral suprachiasmatic nucleus and surrounding the nucleus throughout its rostrocaudal dimension. Neuropeptide Y-immunoreactive and [Met]enkephalin-immunoreactive cells were identified in the intergeniculate leaflet and ventral lateral geniculate nucleus, as were neuropeptide Y-immunoreactive, [Met]enkephalin-immunoreactive, serotonin-immunoreactive and substance P-immunoreactive fibers and terminals. The retinohypothalamic tract innervated both suprachiasmatic nuclei equally; in contrast, retinal innervation to the lateral geniculate nucleus, including the intergeniculate leaflet, was almost exclusively contralateral. Bilateral electrolytic lesions that destroyed the intergeniculate leaflet depleted the suprachiasmatic nucleus of virtually all neuropeptide Y- and [Met]enkephalin-stained fibers and terminals, whereas unilateral lesions reduced fiber and terminal staining by approximately half. Thus, [Met]enkephalin-immunoreactive and neuropeptide Y-immunoreactive cells project equally and bilaterally from the intergeniculate leaflet to the suprachiasmatic nucleus via the geniculohypothalamic tract in degus. This is the first report examining the neural circadian system in a diurnal rodent for which formal circadian properties have been described. The data indicate that the neural organization of the circadian timing system in degus resembles that of the most commonly studied nocturnal rodents, golden hamsters and rats. Armed with such data, one can ascertain differences in the functional organization of the circadian system between diurnal and nocturnal mammals.
Recent evidence suggests that the dorsal raphe nucleus (DRN) of the brainstem is a collection of neuronal clusters having different neurochemical characteristics and efferent projection patterns. To gain further insight into the neuroanatomic organization of the DRN, neuronal populations projecting to the superior colliculus (SC) were mapped in a highly visual rodent, the Mongolian gerbil (Meriones unguiculatus). Retrograde tracers Fluoro-Gold (FG) or cholera toxin subunit-B (CTB) were injected into the superficial layers of the SC, and serotonin (5-hydroxytryptamine, 5-HT) -positive cells were identified by using immunocytochemistry in the FG-injected animals. Based on its projections to the SC, the DRN was divided into five rostrocaudal levels. In the rostral and middle levels of the DRN, virtually all FG-filled cells occurred in the lateral DRN, and 36-55% of 5-HT-immunoreactive (5-HT-ir) cells were also double-labeled with FG. Caudally, FG-filled cells occurred in the lateral, ventromedial, and interfascicular DRN; and 44, 12, and 31% of 5-HT-ir cells, respectively, were also FG-filled. The dorsomedial DRN contained only a small proportion of FG-filled cells at its most caudal level and was completely devoid of FG-filled cells more rostrally. The CTB-injected animals showed a similar distribution of retrogradely labeled cells in the DRN. Topographically, the dorsal tegmental nucleus and the laterodorsal tegmental nucleus appeared to be closely associated with 5-HT-ir cells in the caudal DRN. These results suggest that the lateral DRN and the ventromedial/interfascicular DRN may be anatomically, morphologically, and neurochemically unique subdivisions of the gerbil DRN.
A direct pathway from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in both albino rats and Mongolian gerbils. Following intraocular injection of cholera toxin subunit B (CTB), a diffuse stream of CTB-positive, fine-caliber optic axons emerged from the optic tract at the level of the pretectum/anterior mesencephalon. In gerbils, CTB-positive axons descended ventromedially into the periaqueductal gray, moving caudally and arborizing extensively throughout the DRN. In rats, the retinal-DRN projection comprised fewer, but larger caliber, axons, which arborized in a relatively restricted region of the lateral and ventral DRN. Following injection of CTB into the lateral DRN, retrogradely labeled ganglion cells (GCs) were observed in whole-mount retinas of both species. In gerbils, CTB-positive GCs were distributed over the entire retina, and a nearest-neighbor analysis of CTB-positive GCs showed significant regularity (nonrandomness) in their distribution. The overall distribution of gerbil GC soma diameters ranged from 8 to 22 micrometer and was skewed slightly towards the larger soma diameters. Based on an adaptive mixtures model statistical analysis, two Gaussian distributions appeared to comprise the total GC distribution, with mean soma diameters of 13 (SEM +/-1.7) micrometer, and 17 (SEM +/-1.5) micrometer, respectively. In rats, many fewer CTB-positive GCs were labeled following CTB injections into the lateral DRN, and nearly all occurred in the inferior retina. The total distribution of rat GC soma diameters was similar to that in gerbils and also was skewed towards the larger soma diameters. Major differences observed in the extent and configuration of the retinal-DRN pathway may be related to the diurnal/crepuscular vs. nocturnal habits of these two species.
Identification of retinal ganglion cells the subunit B of cholera toxin: a highly sensitive immunohistochprojecting to the lateral hypothalamic area of the rat emical protocol for revealing fine axonal morphology in adult and
- R K Leak
- R Y Moore
R.K. Leak, R.Y. Moore, Identification of retinal ganglion cells the subunit B of cholera toxin: a highly sensitive immunohistochprojecting to the lateral hypothalamic area of the rat, Brain Res. 770 emical protocol for revealing fine axonal morphology in adult and (1997) 105–114. neonatal brains, J. Neurosci. Methods 65 (1996) 101–112.
The serotonin 5-HT receptorelectron microscope immunocytochemistry study, Exp
- Y Edagawa
- H Saito
- K Abe
Y. Edagawa, H. Saito, K. Abe, The serotonin 5-HT receptorelectron microscope immunocytochemistry study, Exp. Brain Res.
Direct retinal communication transmission by presynaptic 5-HT receptors in the superior 1B with the peri-amygdaloid area
- A S Elliott
- M L Weiss
- A A Nunez
A.S. Elliott, M.L. Weiss, A.A. Nunez, Direct retinal communication
transmission by presynaptic 5-HT
receptors in the superior
1B
with the peri-amygdaloid area, Neuroreport 6 (1995) 806-808.
colliculus of the adult hamster, J. Neurophysiol. 72 (1994) 3-13.
5-HT receptor sub-types: Aspects of their regulation and Rhoades, Serotonin modulates retinotectal and corticotectal converfunction gence in the superior colliculus, Prog
- R D Mooney
- X Huang
- M Y Shi
- C A Bennet-Clarke
- R W Leslie
R.D. Mooney, X. Huang, M.Y. Shi, C.A. Bennet-Clarke, R.W. Leslie, 5-HT receptor sub-types: Aspects of their regulation and Rhoades, Serotonin modulates retinotectal and corticotectal converfunction, Neurochem. Int. 25 (1994) 537–543. gence in the superior colliculus, Prog. Brain Res. 112 (1996) 57–69.
The Rat Brain in Stereotaxic Coordinates, the dorsal raphe nucleus in rats and Mongolian gerbils
- G Paxinos
- D Watson
- J Comp
G. Paxinos, D. Watson, The Rat Brain in Stereotaxic Coordinates, the dorsal raphe nucleus in rats and Mongolian gerbils, J. Comp. 4th Edition, Academic Press, San Diego, CA, 1998. Neurol. 414 (1999) 469–484.
Evidence for retinal extracellular serotonin concentration in the dorsal raphe nucleus: a projection to the midbrain raphe of the cat) microdialysis study in the freely moving cat
- W E Foote
- E Taber
- L Pierce
- Edwards
W.E. Foote, E. Taber-Pierce, L. Edwards, Evidence for retinal extracellular serotonin concentration in the dorsal raphe nucleus: a projection to the midbrain raphe of the cat, Brain Res. 156 (1978) microdialysis study in the freely moving cat, Brain Res. 648 (1994) 135–140. 306–312.
The mechanisms of action of light in the treatment intergeniculate leaflet in the diurnal rodent Octodon degus: Retinal of seasonal affective disorder (SAD) Jung projections and immunocytochemical characterization
- N E Rosenthal
N.E. Rosenthal, The mechanisms of action of light in the treatment intergeniculate leaflet in the diurnal rodent Octodon degus: Retinal of seasonal affective disorder (SAD), in: M.F. Holick, E.G. Jung projections and immunocytochemical characterization, Neuroscience (Eds.), Biologic Effects of Light, Walter de Gruyter, Berlin, 1996, 92 (1999) 1491–1509. pp. 317–324.
A direct retinal projection to the dorsal raphe retina of the Mongolian gerbil, Meriones unguiculatus: an immunonucleus in the rat
- H Shen
- K Semba
H. Shen, K. Semba, A direct retinal projection to the dorsal raphe retina of the Mongolian gerbil, Meriones unguiculatus: an immunonucleus in the rat, Brain Res. 635 (1994) 159–168. cytochemical and electrophysiological study, Vis. Res. 32 (1992)
Light therapy for seasonal affective disorder. A review Topographical distribution of dorsal and median raphe neurons of efficacy projecting to motor, sensorimotor and visual cortical areas in the rat
- B D Waterhouse
- G A Mihaloff
- J C Baack
- D J Woodward
- B Rafferty
B.D. Waterhouse, G.A. Mihaloff, J.C. Baack, D.J. Woodward, B. Rafferty, Light therapy for seasonal affective disorder. A review Topographical distribution of dorsal and median raphe neurons of efficacy, Neuropsychopharmology 2 (1989) 1–22. projecting to motor, sensorimotor and visual cortical areas in the rat,
Topographic to the hypothalamus, anterior thalamus and basal forebrain in organization of rat locus coeruleus and dorsal raphe nuclei: Dishamsters
- B D Waterhouse
- B Border
- L Wahl
- G A Mihailoff
B.D. Waterhouse, B. Border, L. Wahl, G.A. Mihailoff, Topographic
to the hypothalamus, anterior thalamus and basal forebrain in
organization of rat locus coeruleus and dorsal raphe nuclei: Dishamsters, Brain Res. Bull. 26 (1991) 403-411.
Seasonal variations in binding of References An update of variables current in depression research
- P G Pepplinkhuizen
- Mulder
Pepplinkhuizen, P.G. Mulder, Seasonal variations in binding of References An update of variables current in depression research, in: N.E.