Article

Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat

September 1988
The Journal of Comparative Neurology 275(4):511-41

September 1988
275(4):511-41

DOI:10.1002/cne.902750404

Source
PubMed

Authors:

Robert P Vertes

Florida Atlantic University

Ascending projections from the medial pontine reticular formation, the mesencephalic reticular formation, and the median raphe nucleus were examined using the autoradiographic technique. The majority of the ascending fibers labeled after injections of [ ³ H]‐leucine into the nucleus pontis caudalis (RPC) course through the brainstem within the tracts of Forel (tractus fasciculorum tegmenti of Forel) and directly ventral to them. At the caudal diencephalon, Forel's bundle divides into dorsal and ventral components bound primarily for the dorsal thalamus and the subthalamus, respectively. RPC fibers project to several regions involved in oculomotor/visual functions. These include the abducens nucleus, the intermediate gray layer of the superior colliculus (SCi), the anterior pretectal nucleus (APN), the ventral lateral geniculate nucleus (LGNv), and regions of the central gray directly bordering the oculomotor nucleus, the interstitial nucleus of Cajal, and the nucleus of Darkschewitsch. Few, if any, fibers from RPC (or from nucleus pontis oralis‐‐RPO) terminate within the oculomotor nucleus proper. Other sites receiving heavy projections from the RPC include adjacent regions of the pontomesencephalic reticular formation (RF), the parafascicular (PF) and central lateral (CL) nuclei of the thalamus and the fields of Forel/zona incerta (FF‐ZI). RPO fibers also ascend predominantly in Forel's bundle. Other ascending tracts for these fibers are the medial longitudinal fasciculus and the central tegmental tract (CTT). RPO fibers distribute significantly to the same structures of the oculomotor/visual system receiving projections from RPC. The RPO projections to the SCi and the APN are particularly pronounced. RPO fibers terminate heavily in several nuclei located ventrally within the rostral midbrain/caudal diencephalon. These include major dopamine‐containing cell groups (the retrorubral nucleus, the ventral tegmental area, and the substantia nigra‐pars compacta) as well as the interpeduncular nucleus, the lateral mammillary nucleus, and the supramammillary nucleus. Other prominent targets for RPO fibers include the mesencephalic RF, specific regions of the central gray, the PF, the CL, the paracentral and central medial nuclei of the thalamus, and the FF/ZI. The major bundle of the ascending fibers labeled after injections of the mesencephalic reticular formation (MRF) travels within the CTT in a position just lateral to the central gray, but a significant number of labeled axons also course in Forel's bundle. MRF axons project to several nuclei of the thalamus. MRF fibers terminate densely within the PF, the CL, the paracentral, the central medial, the LGNv, and the reticular thalamic nucleus, and less heavily within the paraventricular nucleus, the nucleus reuniens, and the rhomboid nucleus. Other sites receiving pronounced projections from the MRF include the central gray, the SCi, the FF‐ZI, and the subthalamic nucleus. After injections of the median raphe nucleus (MR), labeled axons are seen over a widespread region of the ventral midbrain tegmentum; these axons join the medial forebrain bundles at the caudal diencephalon and continue within them throughout the forebrain. MR fibers distribute heavily to several “limbic” structures, including the interpeduncular nucleus, the medial mammillary nucleus, the VTA, the lateral habenula, the medial preoptic area, the nuclei of the vertical and horizontal limbs of the diagonal band, the septum, the nucleus accumbens, and the hippocampal formation. Possible functions for some of the connections described herein are discussed.

Sustaining wakefulness: Brainstem connectivity in human consciousness

Preprint

Full-text available

Jul 2023

Consciousness is comprised of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that modulate awareness in the human brain, but knowledge about the subcortical networks that sustain arousal is lacking. We integrated data from ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map the connectivity of a subcortical arousal network that we postulate sustains wakefulness in the resting, conscious human brain, analogous to the cortical default mode network (DMN) that is believed to sustain self-awareness. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain by correlating ex vivo diffusion MRI with immunohistochemistry in three human brain specimens from neurologically normal individuals scanned at 600-750 µm resolution. We performed deterministic and probabilistic tractography analyses of the diffusion MRI data to map dAAN intra-network connections and dAAN-DMN internetwork connections. Using a newly developed network-based autopsy of the human brain that integrates ex vivo MRI and histopathology, we identified projection, association, and commissural pathways linking dAAN nodes with one another and with cortical DMN nodes, providing a structural architecture for the integration of arousal and awareness in human consciousness. We release the ex vivo diffusion MRI data, corresponding immunohistochemistry data, network-based autopsy methods, and a new brainstem dAAN atlas to support efforts to map the connectivity of human consciousness. One sentence summary We performed ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map brainstem connections that sustain wakefulness in human consciousness.

The Reticular Formation and the Neuromodulatory Systems

Chapter

Jun 2020

Almost a century ago, Constantin von Economo observed that in patients with encephalitis lethargica lesions in the upper brain stem and posterior hypothalamus impaired consciousness. From lesion studies in cats and anatomical data, the idea arose that the brain stem reticular formation is the origin of the ascending reticular activating system (ARAS) that would operate through the intralaminar nuclei and activate widespread regions of the cerebral cortex. This view of the reticular formation has been extensively modified, and nowadays the reticular formation is viewed as a series of highly specific cell groups, which closely surround the individual motor and sensory nuclei of the brain stem (► Sects. 5.2 and 5.4). The diffuse system, driving arousal and consciousness, is now attributed to the neuromodulatory system, including the serotonergic raphe nuclei, the locus coeruleus and other noradrenergic or adrenergic cell groups and cholinergic cell groups, all close to the reticular formation (► Sects. 5.3 and 5.5). The English terms of the Terminologia Neuroanatomica are used throughout.

The structural connectivity mapping of the intralaminar thalamic nuclei

Article

Full-text available

Jul 2023

The intralaminar nuclei of the thalamus play a pivotal role in awareness, conscious experience, arousal, sleep, vigilance, as well as in cognitive, sensory, and sexual processing. Nonetheless, in humans, little is known about the direct involvement of these nuclei in such multifaceted functions and their structural connections in the brain. Thus, examining the versatility of structural connectivity of the intralaminar nuclei with the rest of the brain seems reasonable. Herein, we attempt to show the direct structural connectivity of the intralaminar nuclei to diencephalic, mesencephalic, and cortical areas using probabilistic tracking of the diffusion data from the human connectome project. The intralaminar nuclei fiber distributions span a wide range of subcortical and cortical areas. Moreover, the central medial and parafascicular nucleus reveal similar connectivity to the temporal, visual, and frontal cortices with only slight variability. The central lateral nucleus displays a refined projection to the superior colliculus and fornix. The centromedian nucleus seems to be an essential component of the subcortical somatosensory system, as it mainly displays connectivity via the medial and superior cerebellar peduncle to the brainstem and the cerebellar lobules. The subparafascicular nucleus projects to the somatosensory processing areas. It is interesting to note that all intralaminar nuclei have connections to the brainstem. In brief, the structural connectivity of the intralaminar nuclei aligns with the structural core of various functional demands for arousal, emotion, cognition, sensory, vision, and motor processing. This study sheds light on our understanding of the structural connectivity of the intralaminar nuclei with cortical and subcortical structures, which is of great interest to a broader audience in clinical and neuroscience research.

Update on temporal lobe‐dependent information processing, in health and disease

Article

Oct 2019

Laetitia Chauvière

The past decade has been characterized by a lot of remodeling in the field of learning and memory. Both of them, often associated with neuronal oscillations, an emergent property of brain networks, are governed by temporal lobe (TL) functional connectivity. An impairment of oscillatory mechanisms indeed often leads to TL‐dependent cognitive deficits. While the classical view assigned the TL a major role in spatial information processing, new theories rather confer to the TL a more general function in cognitive processes beyond space representation. The present review covers, both in humans and in animal models, (i) the updated role of the TL in cognitive processes, addressing current debates in the field and proposing a scenario on how TL structures cooperate in order to bind an integrated representation of afferent information, (ii) the oscillatory mechanisms underlying these TL‐dependent cognitive functions (theta, gamma, sharp wave ripples), and (iii) how TL‐dependent cognition is altered during temporal lobe epilepsy, proposing a scenario on how reorganized TL networks in TLE leads to rhythmopathies and cognitive deficits. Temporal lobe epilepsy (TLE) is a well‐studied neurological disease. Patients do not only suffer from epileptic seizures but also from cognitive and behavioral deficits between their seizures called co‐morbidities. TLE animal models are therefore used to understand how and when these co‐morbidities arise and what their underlying mechanisms are. (219 words)

Chemogenetic inhibition of cells in the paramedian midbrain tegmentum increases locomotor activity in rats

Article

Dec 2015

The Dopaminergic Cells in the Median Raphe Region Regulate Social Behavior in Male Mice

Article

Full-text available

Apr 2024
INT J MOL SCI

According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance. Next, we used chemogenetic technology in mice containing the Cre enzyme under the promoter of the dopamine transporter. With the help of an adeno-associated virus, designer receptors exclusively activated by designer drugs (DREADDs) were expressed in the dopaminergic cells of the MRR to manipulate their activity. Four weeks later, we performed an extensive behavioral characterization 30 min after the injection of the artificial ligand (Clozapine-N-Oxide). Stimulation of the dopaminergic cells in the MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social behavior during social interaction test. No behavioral changes were detected in anxiety, memory or locomotion. All in all, dopaminergic cells were present in both the mouse and human samples from the MRR, and the manipulation of the dopaminergic neurons in the MRR elicited a specific social response.

The Role of the Dopaminergic Cells of the Median Raphe Region in the Behavior of the Male Mice

Preprint

Full-text available

Mar 2024

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

Structural and functional organization of the midline and intralaminar nuclei of the thalamus

Article

Full-text available

Aug 2022

The midline and intralaminar nuclei of the thalamus form a major part of the “limbic thalamus;” that is, thalamic structures anatomically and functionally linked with the limbic forebrain. The midline nuclei consist of the paraventricular (PV) and paratenial nuclei, dorsally and the rhomboid and nucleus reuniens (RE), ventrally. The rostral intralaminar nuclei (ILt) consist of the central medial (CM), paracentral (PC) and central lateral (CL) nuclei. We presently concentrate on RE, PV, CM and CL nuclei of the thalamus. The nucleus reuniens receives a diverse array of input from limbic-related sites, and predominantly projects to the hippocampus and to “limbic” cortices. The RE participates in various cognitive functions including spatial working memory, executive functions (attention, behavioral flexibility) and affect/fear behavior. The PV receives significant limbic-related afferents, particularly the hypothalamus, and mainly distributes to “affective” structures of the forebrain including the bed nucleus of stria terminalis, nucleus accumbens and the amygdala. Accordingly, PV serves a critical role in “motivated behaviors” such as arousal, feeding/consummatory behavior and drug addiction. The rostral ILt receives both limbic and sensorimotor-related input and distributes widely over limbic and motor regions of the frontal cortex—and throughout the dorsal striatum. The intralaminar thalamus is critical for maintaining consciousness and directly participates in various sensorimotor functions (visuospatial or reaction time tasks) and cognitive tasks involving striatal-cortical interactions. As discussed herein, while each of the midline and intralaminar nuclei are anatomically and functionally distinct, they collectively serve a vital role in several affective, cognitive and executive behaviors – as major components of a brainstem-diencephalic-thalamocortical circuitry.

The role of plasticity in the recovery of consciousness

Chapter

Jan 2022

Sergio Bagnato

Disorders of consciousness (DOCs), i.e., coma, vegetative state, and minimally conscious state are the consequences of a severe brain injury that disrupts the brain ability to generate consciousness. Recovery from DOCs requires functional and structural changes in the brain. The sites where these plastic changes take place vary according to the pathophysiology of the DOC. The ascending reticular activating system of the brainstem and its complex connections with the thalamus and cortex are involved in the pathophysiology of coma. Subcortical structures, such as the striatum and globus pallidus, together with thalamocortical and corticothalamic projections, the basal forebrain, and several networks among different cortical areas are probably involved in vegetative and minimally conscious states. Some mechanisms of plasticity that allegedly operate in each of these sites to promote recovery of consciousness will be discussed in this chapter. While some mechanisms of plasticity work at a local level, others produce functional changes in complex neuronal networks, for example by entraining neuronal oscillations. The specific mechanisms of brain plasticity represent potential targets for future treatments aiming to restore consciousness in patients with severe DOCs.

The role of the posterior hypothalamic area in the generation of theta rhythm

Article

Full-text available

Jun 2021

Streszczenie Rytm theta jest jednym z najlepiej zsynchronizowanych wzorców aktywności oscylacyjnej rejestrowanych w mózgach ssaków. U ludzi, rytm ten obserwowany jest podczas snu REM, nawigacji przestrzennej, procesów pamięciowych, analitycznych oraz językowych. Może być również traktowany jako nieswoisty marker stanów patologicznych ośrodkowego układu nerwowego, takich jak choroba Alzheimera czy padaczka. Główną strukturą zaangażowaną w generowanie wzorca aktywności bioelektrycznej, zarówno u ludzi, jak i u gryzoni (najczęściej badanych zwierząt laboratoryjnych), jest formacja hipokampa. Jej funkcjonowanie zależy od współdziałania wielu innych struktur układu nerwowego. Jedną z nich jest obszar tylnego podwzgórza, który jest istotnym elementem układów neuronalnych modulujących zdolność formacji hipokampa do generowania rytmu theta. Przedstawione w artykule wyniki badań podkreślają rolę obszaru tylnego podwzgórza, jako modulatora hipokampalnego rytmu theta, ale wykazują również, że obszar ten jest zdolny do samodzielnego, niezależnego od wpływu innych struktur, generowania rytmicznej aktywności theta.

A Role For Tachykinin 1 Preoptic Neurons In Natural And Anesthetic-Induced Arousal State Regulation

Article

Jan 2020

Sarah Lorraine Reitz

The role of the hypothalamic preoptic area (POA) in arousal state regulation has been studied since the early 20th century. Since then, the POA has been shown to modulate arousal in both natural (sleep and wake) as well as drug-induced (anesthetic-induced unconsciousness) states. While the POA is most known for its role in sleep promotion, populations of wake-promoting neurons within the region have also been identified. However, the complexity and molecular heterogeneity of the POA has made distinguishing these two populations difficult. Though multiple lines of evidence demonstrate that general anesthetics modulate the activity of the POA, the region’s heterogeneity has also made it challenging to determine whether the same neurons involved in sleep/wake regulation also modulate arousal in response to general anesthetics. While a number of studies show that sleep-promoting POA neurons are activated by various anesthetics, recent work suggests this is not universal to all arousal-regulating POA neurons. We hypothesized that the POA’s broad neuronal diversity could mask convergent roles of a subset of neurons in regulating both arousal and anesthesia. In this dissertation, we utilize a neuropeptide, tachykinin 1 (Tac1), as a molecular marker for arousal state-regulating POA neurons and show using EEG/EMG recordings that chemogenetic activation of these POA Tac1 neurons strongly promotes wakefulness over both NREM and REM sleep, consolidating the wake state for hours. Additionally, actigraphy and video recordings demonstrate that POA Tac1 activation increases locomotor activity, with no evidence of enhanced anxiety. We also show that activation of this same population stabilizes the wake state against both isoflurane- and sevoflurane-induced unconsciousness, producing a partial resistance to entering isoflurane anesthesia and a more pronounced ability to exit both isoflurane and sevoflurane hypnosis. Furthermore, activation of POA Tac1 neurons promotes resistance throughout prolonged exposures to isoflurane on both the population and individual level, further supporting their arousal-promoting role. Together, these results demonstrate that POA Tac1 neurons can potently reinforce arousal against both endogenous and drug-induced states of unconsciousness, identifying a subpopulation within the POA that may be shared between the circuits regulating sleep/wake and anesthesia.

Modulation of extracellular noradrenaline in rat cortex by selective serotonin reuptake inhibitors (SSRIs)

Thesis

Jan 1998

Zoë A Hughes

This research project has investigated the modulation of central noradrenergic function in rat cortex by antidepressant drugs. Particular attention has been paid to the type of antidepressants known as the selective serotonin (5-HT) reuptake inhibitors (SSRIs). The therapeutic effects of these drugs are presently attributed exclusively to their inhibition of neuronal uptake of 5-HT. The aim of this work was to investigate whether the SSRIs, fluoxetine and citalopram, modify central noradrenergic function and, if so, was their site of action on noradrenergic neurones? In order to achieve this two techniques were used: the first used microdialysis to measure the concentration of extracellular noradrenaline in vivo, the second looked at the inhibition of [3H]noradrenaline uptake into rat cortical synaptosomes in vitro. In this thesis changes in the concentration of extracellular noradrenaline caused by local infusion of antidepressants in the frontal cortex of rats, were monitored using microdialysis. Fluoxetine and citalopram, as well as the noradrenaline uptake inhibitor, desipramine, increased noradrenaline efflux. To investigate whether inhibition of noradrenaline uptake could contribute to this increase in efflux, the effects of these drugs on synaptosomal [3H]noradrenaline uptake were studied. Because these drugs inhibit [3H]noradrenaline uptake, it is likely that inhibition of noradrenaline uptake contributes to the increase in noradrenaline efflux in vivo. In view of this finding, the possible site(s) of action of these drugs were investigated. An uptake site targeted by SSRIs could be located on serotonergic neurones. The 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), was used as a tool to investigate this possibility. Because a selective lesion of 5-HT neurones did not affect the inhibition of [3H]noradrenaline uptake by any of the drugs, it is unlikely that fluoxetine, citalopram or desipramine were acting at a site on serotonergic neurones. The second possible site of action investigated was one located on noradrenergic neurones. Pretreatment of rats with the noradrenergic neurotoxin, N-(2-chloroethyl)-N-etiyl-2-broinobenzylamine (DSP-4), modified the effects of these antidepressants on noradrenergic function. Low concentrations of desipramine inhibited a smaller proportion of [3H]noradrenaline uptake than in control rats. In contrast, a greater proportion of uptake in the cortex of DSP-4 lesioned rats was sensitive to inhibition by low concentrations of fluoxetine in vitro. The effects of these drugs on noradrenaline efflux in vivo were also changed after DSP-4 pretreatment. The increase in noradrenaline efflux induced by desipramine was greater in DSP-4 treated rats, whereas the fluoxetine-induced increase, apparent in control rats, was not evident after DSP-4. The effects of citalopram were unaffected by DSP-4 treatment, suggesting that SSRIs do not all have the same pharmacological profile and that fluoxetine, but not citalopram, could act at a site on noradrenergic neurones. One additional, but important finding to emerge from work described in this thesis was that, although DSP-4 treatment caused a 70% reduction in tissue noradrenaline content, the concentration of extracellular noradrenaline was increased nearly 2-fold. Results suggest that neurones which survive DSP-4 treatment have a greater rate of noradrenaline release, moreover, released noradrenaline is taken up via low affinity uptake sites. Overall, the experiments in this thesis have exposed marked effects of SSRIs on central noradrenergic function which could contribute to the efficacy of antidepressants hitherto regarded as acting selectively on serotonergic neurones.

Untangling the dorsal diencephalic conduction system: a review of structure and function of the stria medullaris, habenula and fasciculus retroflexus

Article

Full-text available

Jun 2020
BRAIN STRUCT FUNCT

The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retroflexus. The first component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fibers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retroflexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the first review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retroflexus, with particular focus on their anatomy, function and development.

Involvement of supralemniscal nucleus (B9) 5-HT neuronal system in nociceptive processing: A fiber photometry study

Article

Full-text available

Dec 2020

Abstract Nociception is important perception that has harmful influence on daily life of humans. As to main pain management system, some descending pathways are called descending antinociceptive systems (DAS). As main pathways of DAS, it is well known that dorsal raphe (B6/B7) - rostral ventromedial medulla (B3) - spinal dorsal horn includes serotonergic system. However, possible role of supralemniscal (B9) serotonin (5-HT) cell group in pain management is still open question. In this study, we measured activities of B9 5-HT neuronal cell bodies and B9 5-HT neuron-derived axons located in the locus coeruleus (LC) and ventral tegmental area (VTA), which are also main players of pain management, using fiber photometry system. We introduced the G-CaMP6 in B9 5-HT neurons using transgenic mice carrying a tetracycline-controlled transactivator transgene (tTA) under the control of a tryptophan hydroxylase-2 (TPH2) promoter and site-specific injection of adeno associated virus (AAV-TetO(3G)-G-CaMP6). After confirmation of specific expression of G-CaMP6 in the target population, G-CaMP6 fluorescence intensity in B9 group and LC/VTA groups was measured in awake mice exposed to acute tail pinch and heat stimuli. G-CaMP6 fluorescence intensity rapidly increased by both stimuli in all groups, but not significantly reacted by nonnociceptive control stimuli. The present results clearly indicate that acute nociceptive stimuli cause a rapid increase in the activities of B9-LC/B9-VTA 5-HTergic pathways, suggesting that B9 5-HT neurons play important roles in nociceptive processing.

Habenular connections with the dopaminergic and serotonergic system and their role in stress‐related psychiatric disorders

Article

Dec 2019

The habenula (Hb) is a phylogenetically old epithalamic structure differentiated into two nuclear complexes, the medial (MHb) and lateral habenula (LHb). After decades of search for a great unifying function, interest in the Hb resurged when it was demonstrated that LHb plays a major role in the encoding of aversive stimuli ranging from noxious stimuli to the loss of predicted rewards. Consistent with a role as an anti‐reward center, aberrant LHb activity has now been identified as a key factor in the pathogenesis of major depressive disorder. Moreover, both MHb and LHb emerged as new players in the reward circuitry by primarily mediating the aversive properties of distinct drugs of abuse. Anatomically, the Hb serves as a bridge that links basal forebrain structures with monoaminergic nuclei in the mid‐ and hindbrain. So far, research on Hb has focused on the role of the LHb in regulating midbrain dopamine release. However, LHb/MHb are also interconnected with the dorsal (DR) and median (MnR) raphe nucleus. Hence, it is conceivable that some of the habenular functions are at least partly mediated by the complex network that links MHb/LHb with pontomesencephalic monoaminergic nuclei. Here, we summarize research about the topography and transmitter phenotype of the reciprocal connections between the LHb and ventral tegmental area‐nigra complex, as well as those between the LHb and DR/MnR. Indirect MHb outputs via interpeduncular nucleus to state setting neuromodulatory networks will also be commented. Finally, we discuss the role of specific LHb‐VTA and LHb/MHb‐raphe circuits in anxiety and depression.

Selective Functional Interaction Between the Lateral Habenula and Hippocampus During Different Tests of Response Flexibility

Article

Full-text available

Oct 2019

The lateral habenula (LHb) has been shown to play critical roles in a variety of appetitive tasks (e.g., spatial memory and object recognition) that require animals to flexibly respond to changing task conditions. These types of tasks are known to be dependent on hippocampus (HPC) and/or medial prefrontal cortex (mPFC), suggesting that the LHb contributes to the limbic memory circuit. Here we provide new evidence that the LHb and HPC play distinct but complimentary roles in tasks that require flexible responding to changing task conditions. Experiment 1 tested whether the LHb is needed for the performance of a HPC-dependent maze-based spatial delayed alternation task. The importance of interactions between the LHb and HPC to accomplish the same spatial delayed alternation task was tested in Experiment 2 where the LHb and HPC were disconnected both ipsilaterally and contralaterally. Experiment 3 tested LHb’s involvement in a standard behavioral economic task that requires flexible responding (maze-based delayed discounting), a task previously shown to rely on HPC. Results of Experiment 1, revealed that LHb inactivation impairs spatial delayed alternation during asymptotic performance but not during initial learning. Importantly, working memory did not appear to be affected as performance remained above chance levels both during initial learning and asymptotic testing. Experiment 2 showed that ipsilateral and contralateral disconnection of the LHb and HPC led to impaired performance on the spatial delayed alternation task. Impairments were not observed after unilateral inactivation of only one structure. Results of Experiment 3 were similar to our previous report of the effects of HPC inactivation: LHb inactivation impaired delayed discounting. All effects could not be accounted for by changes in reward magnitude discrimination, reward location per se, or sex of the animal. These findings, combined with other recent publications confirms and extends our working hypothesis that the LHb enables adaptive and flexible responding, particularly when established rules must be flexibly applied on a trial by trial basis. Since there are no known direct anatomical connections between LHb and HPC, future research is needed to understand how these structures communicate to enable flexible and rapid responding.

Homo- et hétérosynaptique spike-timing-dependent plasticity aux synapses cortico- et thalamo-striatales

Thesis

Sep 2017

Alexandre Mendes

D’après le postulat de Hebb, les circuits neuronaux ajustent et modifient durablement leurs poids synaptiques en fonction des patrons de décharges de part et d’autre de la synapse. La « spike-timing-dependent plasticity » (STDP) est une règle d’apprentissage synaptique hebbienne dépendante de la séquence temporelle précise (de l’ordre de la milliseconde) des activités appariées des neurones pré- et post-synaptiques. Le striatum, le principal noyau d’entrée des ganglions de la base, reçoit des afférences excitatrices provenant du cortex cérébral et du thalamus dont les activités peuvent être concomitantes ou décalées dans le temps. Ainsi, l’encodage temporal des informations corticales et thalamiques via la STDP pourrait être crucial pour l’implication du striatum dans l’apprentissage procédural. Nous avons exploré les plasticités synaptiques cortico- et thalamo-striatales puis leurs interactions à travers le paradigme de la STDP. Les principaux résultats sont :1. Les « spike-timing-dependent plasticity » opposées cortico-striatales et thalamo-striatales induisent des plasticités hétérosynaptiques. Si la très grande majorité des études sont consacrées à la plasticité synaptique cortico-striatale, peu ont exploré les règles de plasticité synaptique aux synapses thalamo-striatale et leurs interactions avec la plasticité cortico-striatale. Nous avons étudié la STDP thalamo-striatale et comment les plasticités synaptiques thalamo- et cortico-striatales interagissent…

Participation of the Thalamic CM-Pf Complex in Attentional Orienting

Article

Jun 2002

The centre médian-parafascicular (CM-Pf) complex is located at the posterior intralaminar nuclei of the thalamus and forms part of the nonspecific thalamocortical projection system and the internal circuit of the basal ganglia. However, the functional roles of this complex remain to be fully elucidated. Here we have examined whether the CM-Pf complex is involved in the process of covert attention. We trained two macaque monkeys to perform a task in which a visual target stimulus for button release appeared at either the same location as the preceding visual instruction cue (a “validly cued target”) or a location on the opposite side (an “invalidly cued target”). Reaction times (RTs) to a validly cued target were significantly shorter than those to an invalidly cued target, leading to a “validity effect” of about 20 ms. We recorded the activity of 97 neurons in the CM-Pf while the monkeys performed the attention task with the hand that was contralateral to the neuronal recording. Seventy CM-Pf neurons showed task-related activity after the appearance of either the instruction cue or the target stimulus: 33 neurons responded with a prominent short-latency facilitation (SLF), whereas 37 responded with a short-latency suppression followed by a long-latency facilitation (LLF). Most of the SLF neurons responded preferentially to a cue appearing on the contralateral side (76%) and to an invalidly cued target appearing on the contralateral side (61%). In contrast, LLF neurons showed a short-latency suppression after the cue stimulus, regardless of whether the cue appeared on the contra- or ipsilateral side (84%). Inactivating the CM-Pf complex by local injection (1 μl) of the GABA A receptor agonist muscimol (1–5 μg/μl) resulted in a significant increase in the RT to a validly cued target presented on the contra- but not the ipsilateral side. In contrast, inactivating the CM-Pf complex did not affect RTs to invalidly cued targets on either the contra- or the ipsilateral side. Thus the validity effect was abolished only on the contralateral side. We conclude that the CM-Pf complex plays a specific and essential role in the process of attentional orienting to external events occurring on the contralateral side, probably through the projection of primary outputs to the striatum, which is involved in the action-selection mechanisms of the basal ganglia.

The Modulation of Hippocampal Theta Rhythm by the Vestibular System

Article

Nov 2017

The vestibular system is a sensory system that has evolved over millions of years to detect acceleration of the head, both rotational and translational, in three dimensions. One of its most important functions is to stabilize gaze during unexpected head movement; however, it is also important in the control of posture and autonomic reflexes. Theta rhythm is a 3-12 Hz oscillating EEG signal that is intimately linked to self-motion and is also known to be important in learning and memory. Many studies over the last two decades have shown that selective activation of the vestibular system, either using natural rotational or translational stimulation, or electrical stimulation of the peripheral vestibular system, can induce and modulate theta activity. Furthermore, inactivation of the vestibular system has been shown to significantly reduce theta in freely moving animals, which may be linked to its impairment of place cell function as well as spatial learning and memory. The pathways through which vestibular information modulate theta rhythm remain debatable. However, vestibular responses have been found in the pedunculopontine tegmental nucleus (PPTg) and activation of the vestibular system causes an increase in acetylcholine release into the hippocampus, probably from the medial septum. Therefore, a pathway from the vestibular nucleus complex and/or cerebellum to the PPTg, supramammillary nucleus, posterior hypothalamic nucleus and the septum, to the hippocampus, is likely. The modulation of theta by the vestibular system may have implications for vestibular effects on cognitive function and the contribution of vestibular impairment to the risk of dementia.

Nuclear derivatives and axonal projections originating from rhombomere 4 in the mouse hindbrain

Article

Full-text available

Nov 2017
BRAIN STRUCT FUNCT

The r4-derived territory is located in the pontine region of the brainstem, forming a wedge-shaped slice that broadens from the choroidal roof to the ventral midline. R4-derived neuronal populations migrate radially inside and tangentially outside this rhombomere, forming nuclei of the sensorimotor auditory, vestibular, trigeminal and reticular systems. R4-derived fibre tracts contribute to the lateral lemniscus, the trigeminothalamic tracts, the medial tegmental tract and the medial forebrain bundle, which variously project to the midbrain, thalamus, hypothalamus and telencephalon. Other tracts such as the trigeminocerebellar and vestibulocerebellar tracts reach the cerebellum, while the medial and lateral vestibulospinal tracts, and the reticulospinal and trigeminal oro-spinal tracts extend into the spinal cord. Many r4-derived fibres are crossed; they decussate to the contralateral side traversing the midline through the cerebellar, collicular and intercollicular commissures, as well as the supraoptic decussation. Moreover, some fibres enter into the posterior and anterior commissures and some terminals reach the septum. Overall, this study provides an overview of all r4 neuronal populations and axonal tracts from their embryonic origin to the adult final location and target.

Effects of bilateral vestibular deafferentation in rat on hippocampal theta response to somatosensory stimulation, acetylcholine release, and cholinergic neurons in the pedunculopontine tegmental nucleus

Article

Full-text available

Sep 2017
BRAIN STRUCT FUNCT

Vestibular dysfunction has been shown to cause spatial memory impairment. Neurophysiological studies indicate that bilateral vestibular loss (BVL), in particular, is associated with an impairment of the response of hippocampal place cells and theta rhythm. However, the specific neural pathways through which vestibular information reaches the hippocampus are yet to be fully elucidated. The aim of the present study was to further investigate the hypothesised ?theta-generating pathway? from the brainstem vestibular nucleus to the hippocampus. BVL, and in some cases, unilateral vestibular loss (UVL), induced by intratympanic sodium arsanilate injections in rats, were used to investigate the effects of vestibular loss on somatosensory-induced type 2 theta rhythm, acetylcholine (ACh) release in the hippocampus, and the number of cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg), an important part of the theta-generating pathway. Under urethane anaesthesia, BVL was found to cause a significant increase in the maximum power of the type 2 theta (3?6?Hz) frequency band compared to UVL and sham animals. Rats with BVL generally exhibited a lower basal level of ACh release than sham rats; however, this difference was not statistically significant. The PPTg of BVL rats exhibited significantly more choline-acetyltransferase (ChAT)-positive neurons than that of sham animals, as did the contralateral PPTg of UVL animals; however, the number of ChAT-positive neurons on the ipsilateral side of UVL animals was not significantly different from sham animals. The results of these studies indicate that parts of the theta-generating pathway undergo a significant reorganisation following vestibular loss, which suggests that this pathway is important for the interaction between the vestibular system and the hippocampus.

Relaxin' the brain: A case for targeting the nucleus incertus network and relaxin-3/RXFP3 neuropeptide/receptor systems in neuropsychiatric disorders

Article

Full-text available

Sep 2016
BRIT J PHARMACOL

Relaxin‐3 has been proposed to modulate emotional–behavioural functions such as arousal and behavioural activation, appetite regulation, stress responses, anxiety, memory, sleep and circadian rhythm. The nucleus incertus (NI), in the midline tegmentum close to the fourth ventricle, projects widely throughout the brain and is the primary site of relaxin‐3 neurons. Over recent years, a number of preclinical studies have explored the function of the NI and relaxin‐3 signalling, including reports of mRNA or peptide expression changes in the NI in response to behavioural or pharmacological manipulations, effects of lesions or electrical or pharmacological manipulations of the NI, effects of central microinfusions of relaxin‐3 or related agonist or antagonist ligands on physiology and behaviour, and the impact of relaxin‐3 gene deletion or knockdown. Although these individual studies reveal facets of the likely functional relevance of the NI and relaxin‐3 systems for human physiology and behaviour, the differences observed in responses between species (e.g. rat vs. mouse), the clearly identified heterogeneity of NI neurons and procedural differences between laboratories are some of the factors that have prevented a precise understanding of their function. This review aims to draw attention to the current preclinical evidence available that suggests the relevance of the NI/relaxin‐3 system to the pathology and/or symptoms of certain neuropsychiatric disorders and to provide cognizant directions for future research to effectively and efficiently uncover its therapeutic potential. Linked Articles This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc

Cell Discharge Correlates of Posterior Hypothalamic Theta Rhythm Recorded In Anesthetized Rats and Brain Slices

Article

Full-text available

Jun 2016
HIPPOCAMPUS

Kowalczyk et al. (Hippocampus 2014; 24:7-20) were probably the first to conduct a systemic study of posterior hypothalamic area (PHa) theta rhythm in anesthetized rats. They demonstrated that local PHa theta field potentials were tail-pinch resistant and could be generated in urethane-anesthetized rats independently of ongoing hippocampal formation theta rhythm. These in vivo data were also confirmed in PHa slice preparations perfused with cholinergic agonist, carbachol. In the current experiments we extend our earlier observations concerning PHa theta rhythm. Specifically, PHa field potentials were analyzed in relation to the ongoing local cell firing repertoire. Single-unit discharge patterns of cells localized in the posterior hypothalamic and supramammillary nuclei were characterized according to the criteria that was developed previously to classify theta-related cells in the hippocampal formation. The present study demonstrated that in addition to the earlier described theta-related cells (theta-on, theta-off and gating cells) the PHa also contains cells discharging in a very regular manner, which were labelled "timing cells". This type of neuron has not been previously documented. We suggest that "timing cells" form a part of the ascending brainstem synchronizing pathway, provide a regular rhythmic signal which facilitates the transduction of tonic discharges of cells localized in the brain stem into theta-frequency rhythmic discharges. This article is protected by copyright. All rights reserved.

5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception

Article

Dec 2015

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

Article

Full-text available

Oct 2015

Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in support of a role for serotonin as a modulator of hippocampal learning, acting through changes in the synchronicity evoked in several relays of the SAS.

25. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze. Hernández-Pérez JJ, Gutiérrez-Guzmán BE, López-Vázquez MÁ and Olvera-Cortés ME. Front. Pharmacol. 6:250. doi: 10.3389/fphar.2015.00250, 2015.

Article

Full-text available

Jan 2015

María Esther Olvera-Cortés

SWS promoting MHb-IPN-MRN circuit opposes the theta promoting circuit, active wake and REM sleep

Article

Full-text available

Oct 2015

Karin Vadovičová

Hippocampus was disynaptically connected to medial habenula (MHb) in my previous DTI study. Observed probabilistic axonal tracts linked hippocampus to septum, and amygdala to bed nucleus of stria terminalis (BNST). Septum and BNST projected to MHb, then from MHb to pineal gland. Question is what is the MHb doing and why it receives information from hippocampus via septum? Thus, this study explores the connectivity of MHb, predicts its functional role and how it is linked to memory replay. My combination of known findings about septum and MHb connectivity and function led to this circuit-based idea that posterior septum activates MHb, MHb activates interpeduncular nucleus (IPN), and then IPN stimulates MRN and its serotonin release. Proposed hypothesis is that MHb-IPN-MRN circuit promotes slow wave sleep (SWS), high serotonin and low acetylcholine state. Main prediction is that this SWS-promoting circuit reciprocally suppresses the output of the theta-promoting regions, both the active wake-on and REM-on neurons. Theta rhythm is strongest in high acetylcholine states, and is induced by supramamillary area (SUM) medial septum (MS) that project to hippocampus and other theta-coupled regions. The MHb-IPN-MRN pathway likely inhibits also few regions that stimulate the theta-generating SUM and MS, such as the wakefulness promoting nucleus incertus (NI), posterior and lateral hypothalamus (PH, LH), laterodorsal tegmentum (LDT), and the REM sleep promoting LDT neurons. Theta rhythm in wakefulness enables binding information with their spatio-temporal and relational context by hippocampus, while the SWS supports rest, replay and transfer of hippocampally stored interconnected information and their cortical reactivations, e. g. in retrosplenial cortex linked to autobiographic memory or in prefrontal cortex that can combine information from any sources.

Thalamus

Chapter

Jan 2015

The present chapter describes the anatomical organization of nuclei of the thalamus, together with functions considerations. The chapter first discusses some general aspects of thalamic organization including functional subdivisions of the thalamus, the categorization of thalamic afferents as drivers or modulators, and reciprocity in thalamocortical relationships. The chapter then proceeds to individually discuss each of the major nuclei of the thalamus. This includes a description of their cellular properties and relative locations, their afferent and efferent connections, and their functions. The order of presentation is as follows: the lateral geniculate nucleus, the ventral posterior complex, the medial geniculate nucleus, the ventral anterior and ventral lateral nuclei, the ventral medial nucleus, the mediodorsal nucleus, the submedial nucleus, the anterior nuclei, the lateral nuclei, the intralaminar nuclei, the midline nuclei, and the reticular nucleus of thalamus. By comparison with previous chapters on the thalamus in this volume, greater emphasis is placed on the mediodorsal nucleus, the anterior nuclei, and the midline and intralaminar nuclei as main components of the “limbic thalamus,” and recently the subject of intense investigation from both an anatomical and functional perspective. The chapter attempts to dispel the notion that the thalamus is a (mere) relay for the transfer of sensorimotor information to the cortex but rather the thalamus is a vital hub in cortico-cortical and cortico-subcortical communication participating as a full partner in the range of functions generally strictly associated with the cortex.

Median Raphe Stimulation-Induced Motor Inhibition Concurrent With Suppression of Type 1 and Type 2 Hippocampal Theta

Article

Aug 2015

This study investigated behavioral, anatomical and electrophysiological effects produced by electrical stimulation of posterior hypothalamic (PH) or median raphe (MR) nuclei, independently and during combined stimulation of both PH and MR. These three stimulation conditions were applied during spontaneous behavior in an open field and during PH stimulation-induced wheel running, while simultaneously recording hippocampal (HPC) field activity. An additional objective was to determine the effects of MR stimulation on Type 1 movement related theta and Type 2 sensory processing related theta. To achieve the latter, when behavioral studies were completed we studied the same rats under urethane anesthesia and then during urethane anesthesia with the addition of atropine sulfate (ATSO4). Here we demonstrated that electrical stimulation of a localized region of the MR nucleus resulted in a profound inhibition of both spontaneously occurring theta related motor behaviors and the theta related motor behaviors induced by electrical stimulation of the PH nucleus. Furthermore, this motor inhibition occurred concurrently with strong suppression of hippocampal theta field oscillations in the freely moving rat, a condition where the theta recorded is Type 2 sensory processing theta occurring coincidently with Type 1 movement related theta (Bland, 1986). Our results indicate that motor inhibition resulted from stimulation of neurons located in the mid central region of the MR, while stimulation in adjacent regions produced variable responses, including movements and theta activity. The present study provided evidence that the pharmacological basis of the suppression of Type 2 sensory processing HPC theta was cholinergic. However, MR inhibition of PH-induced wheel running was not affected by cholinergic blockade, which blocks Type 2 theta, indicating that MR stimulation-induced motor inhibition also requires the suppression of Type 1 theta.

Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior

Article

Full-text available

Aug 2015

Gilbert Jean Kirouac

This article reviews the anatomical connections of the paraventricular nucleus of the thalamus (PVT) and discusses some of the connections by which the PVT could influence behavior. The PVT receives neurochemically diverse projections from the brainstem and hypothalamus with an especially strong innervation from peptide producing neurons. Anatomical evidence is also presented which suggests that the PVT relays information from neurons involved in visceral or homeostatic functions. In turn, the PVT is a major source of projections to the nucleus accumbens, the bed nucleus of the stria terminalis and the central nucleus of the amygdala as well as the cortical areas associated with these subcortical regions. The PVT is activated by conditions and cues that produce states of arousal including those with appetitive or aversive emotional valences. The paper focuses on the potential contribution of the PVT to circadian rhythms, fear, anxiety, food intake and drug-seeking. The information in this paper highlights the potential importance of the PVT as being a component of the brain circuits that regulate reward and defensive behavior with the hope of generating more research in this relatively understudied region of the brain. Copyright © 2015. Published by Elsevier Ltd.

Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness

Article

May 2024
Sci Transl Med

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.

Neuronal degeneration in the forebrain produced by amphetamine, methamphetamine and fenfluramine

Chapter

Dec 2009

A midline thalamic circuit determines reactions to visual threat

Article

Full-text available

May 2018
NATURE

How our internal state is merged with our visual perception of an impending threat to drive an adaptive behavioural response is not known. Mice respond to visual threats by either freezing or seeking shelter. Here we show that nuclei of the ventral midline thalamus (vMT), the xiphoid nucleus (Xi) and nucleus reuniens (Re), represent crucial hubs in the network controlling behavioural responses to visual threats. The Xi projects to the basolateral amygdala to promote saliency-reducing responses to threats, such as freezing, whereas the Re projects to the medial prefrontal cortex (Re→mPFC) to promote saliency-enhancing, even confrontational responses to threats, such as tail rattling. Activation of the Re→mPFC pathway also increases autonomic arousal in a manner that is rewarding. The vMT is therefore important for biasing how internal states are translated into opposing categories of behavioural responses to perceived threats. These findings may have implications for understanding disorders of arousal and adaptive decision-making, such as phobias, post-traumatic stress and addictions.

Differential and complementary roles of medial and lateral septum in the orchestration of limbic oscillations and signal integration

Article

Oct 2017

Marian Tsanov

Anatomical differences between the medial and lateral septum have associated these nuclei with dissimilar functional roles and behaviors. While the medial septum has been implicated, predominantly, in theta rhythm generation along the septo-hippocampal axis, the lateral septum has mainly been investigated in the context of septo-hypothalamic dialogue. Recent advances suggest that medial and lateral septum are more closely functionally-related than previously appreciated. Here, we explore the hypothesis that the medial septum mediates ascending septo-hippocampal theta propagation, while the lateral septum processes a descending hippocampo-septal and septo-hypothalamic reinforcement signal that mediates navigation during motivated behavior. The generation and propagation of theta rhythm is critical for the initiation of exploratory behavior. Indeed theta signal processing of medial and lateral septum nuclei may well be involved in the integration of spatial, rewarding and locomotor signals across different brain networks. We review here the structural features, anatomical connectivity and functional properties of the medial and lateral septum. We discuss the heterogeneous anatomy of the lateral septum, which is composed of diverse sub-regions with distinct ascending and descending projections, and we relate the physiological characteristics of septal nuclei to their functional relationships with the hippocampal formation, the hypothalamus, and the brainstem reticular formation during motivated spatial navigation.

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

Article

Jun 2017

The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures. An overview of lateral habenula efferent connections is given followed by some details about the projections from LHb to a number of structures. In considering the afferent and efferent connections of the LHb some attention is given to the relative validity of regarding it as a bi-partite structure featuring ‘limbic’ and ‘pallidal’ parts. The paper ends with some concluding remarks about the relative place of the LHb in adaptive behaving.

Anatomy of the central serotoninergic projection systems

Article

Jan 2000

Serotoninergic neurons are integral parts of central and/or peripheral nervous networks in diverse forms of invertebrates and vertebrates (Parent 1981a,b), suggesting that these neurons provide animals - across phylogeny - with capacities essential for adapting to changing internal and/or external demands. Clues as to their functional role(s) may already be gained from their morphology: giant metacerebral serotoninergic neurons in molluscs have abundantly collateralized axons (Cottrell 1977) as do some of the large multipolar, extensively ramifying serotoninergic neurons of the mammalian raphe nuclei/ extraraphe reticular 5-HT cell groups (Waterhouse et al. 1986; Vertes 1991; Van Boeckstaele et al. 1993; Vertes and Kocsis 1994; Holmes et al. 1994), implying that they innervate multiple target networks along the neuraxis. This enables them to coordinate and harmonize activities (or response properties) in diverse networks with state-dependent determinants such as the prevailing level of central motor tone, (somato)-sensory processing and autonomic regulation across the sleep/wake cycle (Jacobs and Fornal 1993). By way of abundantly collateralizing, a limited number of neurons are capable of modulating electrical activity and afferent input responsivity in multiple targets in a coordinate fashion. Therefore, certain serotoninergic neurons of the brainstem represent archetypical reticular-type multipolar neurons which resemble the Golgi type 1 neurons of the brainstem reticular core described by Scheibel and Scheibel(1958).

The Thalamostriatal Systems in Normal and Disease States

Chapter

Jan 2017

The existence of the thalamostriatal projection has long been known, but the functional role of this system remains enigmatic. The thalamostriatal system originates from two main groups of thalamic nuclei: the centromedian/parafascicular (CM/Pf) complex and the non-CM/Pf thalamic nuclei. In addition to their differences in thalamic origin, these two thalamostriatal systems display striking differences in their pattern of termination, synaptic properties, and glutamate receptors expression. The responses of striatal neurons to CM/Pf activation are complex and likely involve intrastriatal GABAergic networks. Behaviorally, the CM/Pf-striatal system is involved in attention-related cognitive processes. Through regulation of striatal cholinergic interneuron responses to salient stimuli, the CM/Pf-striatal system contributes to behavioral switching and response biases for reward-oriented actions and learning. Because the CM/Pf complex degenerates in Parkinson's disease and Huntington's chorea, this nondopaminergic pathology may underlie attention-related cognitive deficits in these disorders. The CM/Pf complex is a promising neurosurgical target for Tourette's syndrome and possibly Parkinson's disease.

The Thalamostriatal System and Cognition

Chapter

Nov 2016

The basal ganglia play a critical role in a wide range of cognitive functions. Consequently, neurodegenerative diseases that affect the basal ganglia, such as Parkinson’s disease (PD) and Huntington’s disease (HD), are commonly associated with cognitive impairments. Although dysfunction of the relationships between the prefrontal cortex and the caudate nucleus is likely to be involved in these deficits, data collected over the past decade strongly suggest that the thalamostriatal system from the centromedian (CM) and parafascicular (PF) nuclei is another important regulator of cognitive functions in the basal ganglia. The fact that the CM/PF undergoes severe degeneration in HD and PD further supports the possible contribution of the thalamostriatal system pathology to cognitive dysfunctions in these disorders.

Pattern of Distribution of Serotonergic Fibers to the Amygdala and Extended Amygdala in the Rat: 5-HT projections to the amygdala and BST

Article

May 2016
J COMP NEUROL

As well recognized, serotonergic (5-HT) fibers distribute widely throughout the forebrain, including the amygdala. Although a few reports have examined the 5-HT innervation of select nuclei of the amygdala in the rat, no previous report has described overall 5-HT projections to the amygdala in the rat. Using immunostaining for the serotonin transporter, SERT, we describe the complete pattern of distribution of 5-HT fibers to the amygdala (proper) and to the extended amygdala in the rat. Based on its ontogenetic origins, the amygdalar was subdivided into two major parts: pallial and subpallial components, with the pallial component further divided into superficial and deep nuclei (Olucha-Bordonau et al., 2015). SERT+ fibers were shown to distribute moderately to densely to the deep and cortical pallial nuclei, but, by contrast, lightly to the subpallial nuclei. Specifically, (1) of the deep pallial nuclei, the lateral, basolateral and basomedial nuclei contained a very dense concentration of 5-HT fibers; (2) of the cortical pallial nuclei, the anterior cortical and amygdala-cortical transition zone, rostrally, and the posteromedial and posterolateral nuclei, caudally, contained a moderate concentration of 5-HT fibers; and (3) of the subpallial nuclei, the anterior nuclei and the rostral part of the medial (Me) nuclei contained a moderate concentration of 5-HT fibers, whereas caudal regions of Me as well as the central nuclei and the intercalated nuclei contained a sparse/light concentration of 5-HT fibers. Regarding the extended amygdala (primarily the bed nucleus of stria terminalis, BST), on the whole, the BST contained moderate numbers of 5-HT fibers, spread fairly uniformly throughout BST. The findings were discussed with respect to a critical serotonergic influence on the amygdala, particularly on the basal complex, and extended amygdala in the control of states of fear and anxiety. This article is protected by copyright. All rights reserved.

Sensory responses of neurons of the medial septal area during theta activity modulation by alpha2-adrenoceptor agonist clonidine

Article

Nov 2003
ZH VYSSH NERV DEYAT+

It was shown by us earlier that bilateral intracerebroventricular injection of alpha2-adrenoreceptor agonist clonidine produced a dose-dependent effect on theta oscillations in the septohippocampal system of awake rabbits. A relatively low dose of clonidine (0.5 mug) attenuated and a high dose (5 mug) significantly enhanced the rhythmic activity. It was suggested that the effect of the low dose of clonidine is mediated by presynaptic alpha2-adrenoreceptors were as postsynaptic alpha2-adrenoreceptors. In this article sensory neuronal responses in the medial septal area (MS) were analyzed against the background of the theta activity modulation by different clonidine doses. Different effects of the low and high doses of the agonist were revealed. The low dose of clonidine (0.5 mug in 5 mul into each lateral ventricle) which produced a decrease in the theta activity resulted in attenuation of excitation and enhancement of inhibition, i.e., the number of activating effects significantly decreased and inhibitory responses were more frequent and distinct. The high dose of clonidine (5 mug in 5 mul) which produced a sharp increase in the theta activity led to a significant decrease in the reactions of the MS cells to sensory stimuli (from 76.8% in the control to 45% under clonidine) independently on the initial reaction character. Persisted excitatory and inhibitory responses became less distinct than the initial ones except single excitatory reactions. The results suggest that alpha2-adrenoreceptors are involved in the control of the sensory reactivity of MS neurons. A sharp decrease in neuronal reactivity during stable rhythmical oscillations developing under the influence of high dose of clonidine confirm the role of the theta rhythm in the septohippocampal system as an active filter in information selection and registration.

Autoregulation of serotonin neurons: Role in antidepressant drug action

Article

Sep 1999

Ascending Noradrenergic and Serotonergic Systems in the Human Brainstem

Chapter

Jan 1995

Together with Istvan Törk, we have examined the morphology and distribution of noradrenergic (Baker et al., 1989) and serotonergic neurons in the human brain (Törk and Hornung, 1990; Baker et al, 1991a; Baker et al., 1991b). As in other species, these neurons are confined to anatomically distinct regions. In rats, histofluorescent and immunohistochemical studies have shown that both noradrenergic (Morrison et al., 1978; Levitt et al., 1984) and serotonergic (Lidov et al., 1980) fibers project diffusely to all regions of the cerebral cortex. Although there is variation in the pattern of cortical arborization (Levitt and Moore, 1978; Morrison et al., 1978; Lidov et al., 1980; Steinbusch, 1981), both systems have uniform density of fibers which does not vary substantially across neocortical regions (Morrison et al., 1978; Lidov et al., 1980; Levitt et al., 1984). However in primates, noradrenergic and serotonergic afferents to the cortex show regional and laminar innervation patterns which have a high degree of specificity not found in the rat (Lewis et al., 1986). It has been postulated that these two systems are counteractive (Brodie and Shore, 1957). Noradrenergic neurons have been shown to fire frequently during watchfulness and vigilance whereas serotonergic neurons are quiescent during the same activity in cats (Jacobs and Azmitia, 1992).

Neuronal Networks That Control the Septal Pacemaker System: Synaptic Interconnections Between the Septal Complex, Hippocampus, Supramammillary Area, and Median Raphe

Chapter

Jan 2000

This chapter outlines the synaptic interconnections of neurochemically characterized neuronal cell groups located in the medial septum diagonal band of Broca (MSDB), supramammillary area (SUM), and median raphe nucleus (MR) that are involved directly and indirectly via the MSDB GABAergic and cholinergic pacemaker neurons, in the subcortical regulation of hippocampal theta rhythm activity. Furthermore, data will be presented regarding the way in which the hippocampal formation might regulate the activity of spontaneously bursting SUM neurons. Although the chapter contains descriptions of each experiment, the methodological details will only be given for those procedures that are not generally used.

The Basal Forebrain Cholinergic System: An Evolving Concept in the Neurobiology of the Forebrain

Chapter

Jan 1991

The basal forebrain cholinergic system (BFCS) is the cholinergic component of a broader population of conspicuous neurons in the basal forebrain, recently retermed the basal forebrain magnocellular complex (BFMC) (Hedreen et al., 1984; Koliatsos et al., in press, a). These neurons, which are large (15–18 × 20–30 μm in the rat; ca. 40 × 50 μm in the human), isodendritic, and intensely basophilic, are located in the medial septum, diagonal band of Broca (DBB), substantia innominata, and substriatal gray substance (Kimura et al., 1981; Hedreen et al., 1983; Mesulam et al., 1983b, 1984; Arendt et al., 1986; Dinopoulos et al., 1986; Mesulam and Geula, 1988). Individual cells of the BFMC project to restricted zones within cortex (Table I) (iso- and mesocortex) and limbic structures (hippocampus, piriform cortex, basolateral amygdala) and to the olfactory bulb. In various telencephalic targets of the system, terminal fields of these cells are organized differently, both in terms of cholinergic fiber densities and the extent of terminal domains of individual neurons (Koliatsos et al., in press, a).

Projections of the median raphe nucleus in the rat

Article

May 1999
J COMP NEUROL

No previous report in any species has examined comprehensively the projections of the median raphe (MR) nucleus with modern tracing techniques. The present report represents an in depth analysis of the projections of MR by use of the anterograde anatomical tracer Phaseolus vulgaris-leucoagglutinin. MR fibers descend along the midline within the brainstem and mainly ascend within the medial forebrain bundle in the forebrain. MR fibers distribute densely to the following brainstem/forebrain sites: caudal raphe nuclei, laterodorsal tegmental nucleus, dorsal raphe nucleus, interpeduncular nucleus, medial mammillary body, supramammillary nucleus, posterior nucleus and perifornical region of the hypothalamus, midline and intralaminar nuclei of thalamus, dopamine-containing cell region of medial zona incerta, lateral habenula, horizontal and vertical limbs of the diagonal band nuclei, medial septum, and hippocampal formation. Virtually all of these structures lie on or close to the midline, indicating that the MR represents a midline/para-midline system of projections. Overall, MR projections to the cortex are light. MR projects moderately to the perirhinal, entorhinal and frontal cortices, but sparingly to remaining regions of cortex. A comparison of MR with dorsal raphe (DR) projections (Vertes RP. 1991. J Comp Neurol 313:643–668) shows that these two major serotonin-containing cell groups of the midbrain distribute to essentially nonoverlapping regions of the forebrain; that is, the MR and DR project to complementary sites in the forebrain. A direct role for the MR in the desynchronization of the electroencephalographic activity of the hippocampus and its possible consequences for memory-associated functions of the hippocampus is discussed. J. Comp. Neurol. 407:555–582, 1999.

Hippocampal theta rhythm of REM sleep

Article

Jul 2011

Robert P Vertes

The theta rhythm of the hippocampus is a large-amplitude (1–2 mV), nearly sinusoidal oscillation of 5 to 12 Hz. Theta is present in the hippocampus of the rat during the exploratory movements of waking and continuously throughout REM sleep. In early reports, we identified neurons of the nucleus pontis oralis (RPO) of the pons that discharged in association with the theta of waking and REM sleep, and subsequently showed that electrical stimulation or carbachol injections into the RPO very effectively elicited theta. These findings indicated that RPO was the brain-stem source for the generation of theta. In related studies, we described an ascending RPO to septohippocampal system routed through the hypothalamic supramammillary nucleus controlling theta, and further demonstrated that the serotonin-containing median raphe (MR) nucleus desynchronized the hippocampal EEG – or blocked theta. The latter indicates that theta, like other events of REM sleep, is subject to aminergic modulation; that is, the suppression of MR activity during REM releases theta in that state. Theta serves a well recognized role in memory processing in waking. We suggest that theta does not serve the same function in REM sleep (memory processing), but rather theta (of REM) is a by-product of the intense forebrain activation of REM sleep, which serves the important function of maintaining the minimum requisite levels of activity periodically throughout sleep to ensure and promote recovery from sleep.

Thalamus

Article

Jan 2004

Efferent and afferent connections of the dorsal and median raphe nuclei in the rat

Article

Jan 2008

It is well established that the brainstem contains discrete groups of serotonin-containing neurons with extensive axonal processes that distribute throughout the neuroaxis. Serotonergic neurons have been implicated in a range of functions prominently including the modulation of various events and states of sleep. We describe the efferent and afferent projections of the dorsal raphe (DR) and the median raphe (MR) nuclei. DR fibers distribute widely throughout the forebrain to dopamine-containing nuclei of the ventral midbrain, the lateral hypothalamus, the midline thalamus, amygdala, the dorsal and ventral striatum and adjoining regions of the basal forebrain, and most of the cortex. In contrast to the DR, the MR is a midline/paramidline system of projections. Specifically, MR fibers mainly distribute to forebrain structures lying on or close to the midline including the medial mammillary and supramammillary nuclei, posterior and perifornical nuclei of hypothalamus, midline and intralaminar nuclei of thalamus, lateral habenula, medial zona incerta, diagonal band nuclei, septum and hippocampus. Overall, MR projections to the cortex are light. With few exceptions, DR and MR project to separate, non-overlapping regions of the forebrain - or, in effect, DR and MR share the serotonergic innervation of the forebrain. Although their outputs are distinct, DR and MR receive common sets of afferent projections from limbic cortices, the medial and lateral preoptic areas, lateral habenula, the perifornical, lateral and dorsomedial nuclei of hypothalamus, and several brainstem nuclei prominently including the midbrain and pontine central gray, locus coeruleus, laterodorsal tegmental nucleus and caudal raphe groups. In addition to common afferents, DR receives significant projections from bed nucleus of stria terminalis, lateral septum, diagonal band nuclei, substantia nigra and the tuberomammillary nucleus, while MR receives distinct projections from the medial septum, mammillary nuclei and the interpeduncular nucleus. There are few projections from the amygdala to either DR or MR. In effect, the DR and MR are positioned to integrate of vast array of information from the brainstem and limbic forebrain and through their extensive axonal network influence virtually all parts of the neuro.

The Serotonin and Tachykinin Systems

Article

Dec 2004

The relationship between dreaming, sleep and memory consolidation.

Poster

May 2014

Design, Background and Pilot Data of Master Thesis. Please see the now available preprint: https://www.biorxiv.org/content/early/2018/05/17/323667

The Efferent Projections From the Reticular Formation and the Locus Coeruleus Studied by Anterograde and Retrograde Axonal Transport in the Rat

Article

Full-text available

Dec 1985
J COMP NEUROL

Following injections of [³H]leucine into the formatio reticularis gigantocellularis (Rgc), reticularis pontis caudalis (Rpc), reticularis pontis oralis (Rpo), reticularis mesencephali (Rmes), or the locus coeruleus (LC) of the rat, autoradiographic study revealed prominent reticuloreticular projections from all areas and secondary projections onto cranial nerve motor nuclei from most areas within the brain stem. Common long descending projections extended the full length of the spinal cord terminating in the ventromedial ventral horn and intermediate zone and more sparsely in the base of the dorsal horn and (particularly from Rgc) the region of the motoneurons. Common long ascending projections extended into the forebrain via Forel's tegmental fascicles. A dorsal branch of fibers innervated the intralaminar and midline nuclei of the thalamus. The major fiber system continued forward through Forel's fields and ascended into the pallidum from Rpo, Rmes, and LC and into the neostriatum from Rmes and LC. Fascicles from all areas also ascended in the medial forebrain bundle through the lateral hypothalamus to the lateral preoptic area, substantia innominata, and nuclei of the diagonal band. From Rpo, Rmes, and LC, fibers continued forward to reach the cerebral cortex, where the innervation was sparse and discrete from Rpo and Rmes but moderate and ubiquitous from LC.

The laminar origin and distribution of the crossed tectoreticular pathways

Article

Full-text available

Oct 1981

The superior colliculus is the source of a prominent descending pathway which crosses the midline in the mesencephalon and projects to the paramedian pontine reticular formation. The primary goal of the present study was to identify the cells in the superior colliculus of the grey squirrel which give rise to this pathway by using a combination of anterograde and retrograde tracing techniques. Results from the anterograde studies demonstrated the course and terminal distribution of this pathway and suggested that its laminar origin is the intermediate grey layer, stratum griseum intermediale. The retrograde studies were used to confirm the results of the anterograde experiments and to provide a more quantitative estimate of the laminar distribution of the cells which give rise to this pathway. In most cases, over 90% of the cells retrogradely labeled following injections of horseradish peroxidase along the course of this pathway were located in the intermediate grey lamina. This origin is in contrast to that of the ipsilateral tectoreticular pathway which originates primarily in stratum griseum profundum (Holcombe, V., and W. C. Hall (1981) Neuroscience 6: 255-260) and suggests that these two grey layers of the deep tectum are functionally distinct.

Serotonin Neurons of the Midbrain Raphe: Ascending Projections

Article

Full-text available

Aug 1978

The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.

Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum

Article

Full-text available

Aug 1978

In this study the location of dopamine (DA) neuron perikarya in the rostral mesencephalon of the rat was determined using the glyoxylic acid fluorescence histochemical technique. Subsequently the topography of the projection of these mesencephalic neurons on the basal forebrain and striatum was analyzed using the anterograde transport-autoradiographic tracing method and the retrograde transport-horseradish peroxidase (HRP) technique. The results of these anatomical studies were correlated with the biochemical and histochemical studies presented in previous reports (Moore, '78; Fallon and Moore, '78; Fallon et al., '78) to provide the following conclusions. The topography of the DA neuron projection of the basal forebrain and neostriatum is organized in three planes, dorsal-ventral, medial-lateral and anterior-posterior. DA cells are found almost exclusively in the substantia nigra (SN) and ventral tegmental area (VTA). Ventral cells of the SN and VTA project to the dorsal structures of the basal forebrain such as the septum, nucleus accumbens and neostriatum. The latter includes some DA cells located ventrally in the pars reticulata of the SN. Dorsal cells project to ventral structures. The medial-lateral topography is organized such that the medial sectors of the SN-VTA area project to the medial parts of nuclei in the basal forebrain and neostriatum whereas lateral sectors of the SN-VTA area project to the lateral parts of nuclei in the basal forebrain and neostriatum. An anterior-posterior topography also is evident such that anterior parts of the SN-VTA project anteriorly whereas the posterior SN-VTA projects more posteriorly in these areas. These observations are consistent with the view that the DA neurons of the SN-VTA complex form a single nuclear group with a highly topographically organized projection innervating not only deep nuclei of the telencephalon but allocortical structures as well.

WITHDRAWN: References

Chapter

Jan 1982

Major projections of the reticular formation

Article

Jan 1985

Evidence for the existence of monoamine-containing neurons in the central nervous system: I. Demonstration of monoamine in the cell bodies of brainstem neurons

Article

Jan 1964
Acta Physiol Scand Suppl

Brainstem Modulation of the Hippocampus

Chapter

Jan 1986

Robert P Vertes

Our interest in examining the role of the brainstem in the modulation of the hippocampus developed from an early identification of a population of brainstem reticular cells with activity highly correlated with the theta rhythm of the hippocampus (Vertes, 1979). We found, for instance, that cells of the pontine tegmental field (primarily nucleus pontis oralis) discharged selectively during the theta-associated states of waking-movement and REM sleep (in the rat) and exhibited several additional characteristics in common with hippocampal theta. We suggested that these pontine reticular neurons were directly involved in generating the theta rhythm.

Untersuchungen u die;ber die Haubenregion und ihre oberen Verknu die;pfungen im Gehirn des Menschen und einiger Sa die;ugetiere, mit Beitra die;gen zu den Methoden der Gehirnuntersuchungen

Article

Jan 1877
Arch Psychiatr Neurol Sci

August Forel

Ascending Fibers in Brain Stem Reticular Formation of Cat

Article

Jul 1955
Arch Neurol Psychiatr

Alf Brodal

Moruzzi and Magoun40 in 1949 demonstrated that stimulation of the brain stem of cats desynchronizes and activates the EEG in a manner paralleling arousal from sleep or alerting to attention. This effect was obtained from the medial bulbar reticular formation, pontine and midbrain tegmentum, dorsal hypothalamus, and subthalamus. From their electrophysiologic observations the authors assumed the structural substrate of the "brain stem activating system" to be a series of ascending reticular relays, which are activated by collaterals from sensory paths. The observations of Moruzzi and Magoun40 have subsequently been confirmed and extended by Magoun and his co-workers. The reticular activating system has been identified in the brain stem of the monkey,17 and continued experimental research * has lent support to the assumption that the reticular activating system of the brain stem is "made up of a series of ascending relays coursing forward from the reticular formation of the

Reticular Formation of the Brain

Article

Nov 1958

P. G. R.

A study of afferent input to the inferior olivary complex in the rat by retrograde axonal transport of horseradish peroxidase

Article

Nov 1977
J COMP NEUROL

Under direct visualization, minute amounts of horseradish peroxidase were injected by controlled air pressure through glass micropipettes into the inferior olive of the albino rat. Well localized unilateral injections were obtained, without damage to other brainstem areas or spread into the adjacent reticular formation. After 24 to 36 hours, the entire brain and spinal cord were examined by light microscopy for labelled neurons supplying afferents to the inferior olive. With few exceptions, labelled somata rostral to the inferior olive were found ipsilateral to the injection site, the greatest number occurring in the subparafascicular nucleus and central gray substance around the caudal third ventricle, in the N. of Forel's field, Nn. of Darkschewitsch and Cajal, and adjacent reticular formation, and in the Edinger-Westphal nucleus. Labelled cells were also noted in the sensorimotor cortex, red nucleus, peri-aqueductal gray and all subdivisions of the pretectal complex. Caudal to the olive, labelled neurons were located primarily on the contralateral side in the lateral reticular nucleus, dorsal column nuclei and nucleus proprius of the spinal cord. At the level of the olive, numerous labelled cells occurred bilaterally, but mainly contralateral to the injection site in the lateral and interpositus nuclei of the cerebellum. A smaller number were seen in the N. prepositus hypoglossi and in the medial and spinal subdivisions of the vestibular complex ipsilaterally, in the N. spinal tract of V contralaterally, and in the gigantocellular reticular nucleus bilaterally. A few neurons in the N. raphe obscurus were also labelled. No positive cells were found in the caudate nucleus, globus pallidus, locus coeruleus, or medial cerebellar nucleus. The results are compared and contrasted, region by region, with previous studies of afferent olivary pathways and, where possible, correlations are made with physiologic data.

Some ascending pathways in the brain stem reticular formation

Article

Jan 1958

This is a report of several neuroanatomic studies in the cat in which axon degeneration resulting from electrolytic lesions in the brain stem reticular formation was traced through the use of the Nauta-Gygax silver stain method. A widespread extralemniscal pathway was found to ascend, as a component of Forel's tractus fasciculorum, from the medial and magnocellular region of the medullary and pontine reticular formation to a diffuse termination in the tegmental reticular formation, superior colliculus, thalamic and subthalamic nuclei. Other evidence suggests that Forel's system contains ascending projection pathways from both medial and lateral regions of the bulbar reticular formation. An extensive mesencephalic region projects to the hypothalamus, preoptic, and septal nuclei via the dorsal longitudinal fasciculus. This projection system receives fibers from spinal and trigeminal cell groups as well as ascending reticular projections. Being reciprocally connected with the limbic system, it appears to the authors to represent a neural mechanism of homeostatic control over endocrine and autonomic function. 46 refs. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Structural substrates for integrative patterns in the brain stem reticular core

Article

Jan 1958

Using Golgi methods almost exclusively the brain stems of over "4000 cats, dogs, mice and rats, and a few young macaques" were studied in an attempt to construct a "total image" of the core of the brain stem. Collateral fibers from the long ascending systems, such as the spinal lemniscus, were found to penetrate the reticular formation and the resulting dendritic arbors running parallel to the afferents of the reticular system synapse with them during this parallel course. The authors see little possibility of maintained specificity of input, although some kind of segmental structure is apparently maintained. Typical reticular axons, regardless of position, appear to have frequent collaterals emitted over their entire course, the length of these collaterals varying greatly. 34 refs. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Serotonergic Innervation of the Forebrain in the North American Opossum; pp. 196–212

Article

Feb 1985
BRAIN BEHAV EVOLUT

The forebrain distribution of axons showing serotonin-like immunoreactivity was studied in the North American opossum. Serotonergic innervation of the hypothalamus was extensive, particularly within the ventromedial nucleus, the periventricular nucleus and the rostral supraoptic nucleus. Serotonergic axons were also present within the fields of Forel and zona incerta, but they tended to avoid parts of the subthalamic nucleus. In the thalamus serotonergic innervation was dense within the midline nuclei (e.g. the central, intermediate dorsal and rhomboid nuclei) and the ventral lateral geniculate nucleus, but relatively sparse in some of the nuclei more readily associated with specific functions (e.g. the ventrobasal nucleus). Serotonergic axons innervate most areas of the rostral and dorsal forebrain. Areas containing the heaviest innervation included the interstitial nucleus of the stria terminalis and the lateral septal nucleus. Serotonergic innervation of the neocortex varied markedly from region to region and within different layers of the same regions. The retrograde transport of True Blue combined with immunofluorescence for localization of serotonin revealed that serotonergic axons within the forebrain arise mainly within the dorsal raphe and superior central nuclei, but that some originate within the midbrain and pontine reticular formation and the locus coeruleus, pars alpha. Neurons of the raphe magnus and obscurus also innervate the forebrain, but few of them are serotonergic. The use of horseradish peroxidase as a retrograde marker provided evidence that raphe projections to the forebrain are topographically organized. Our results suggest that serotonergic projections to the forebrain, like those to the spinal cord, are connectionally heterogeneous.

An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat

Article

Jun 1978
J COMP NEUROL

The differential projections from the dorsal raphe and median raphe nuclei of the midbrain were autoradiographically traced in the rat brain after 3H-proline micro-injections. Six ascending fiber tracts were identified, the dorsal raphe nucleus being the sole source of four tracts and sharing one with the median raphe nucleus. The tracts can be classified as those lying within the medial forebrain bundle (dorsal raphe forebrain tract and the median raphe forebrain tract) and those lying entirely outside (dorsal raphe arcuate tract, dorsal raphe periventricular tract, dorsal raphe cortical tract, and raphe medial tract). The dorsal raphe forebrain tract lies in the ventrolateral aspect of the medial forebrain bundle (MFB) and projects mainly to lateral forebrain areas (e.g., basal ganglion, amygdala, and the pyriform cortex). The median raphe forebrain tract lies in the ventromedial aspect of the MFB and projects to medial forebrain areas (e.g., cingulate cortex, medial septum, and hippocampus). The dorsal raphe cortical tract lies ventrolaterally to the medial longitudinal fasciculus and projects to the caudate-putamen and the parieto-temporal cortex. The dorsal raphe periventricular tract lies immediately below the midbrain aqueduct and projects rostrally to the periventricular region of the thalamus and hypothalamus. The dorsal raphe arcuate tract curves laterally from the dorsal raphe nucleus to reach the ventrolateral edge of the midbrain and projects to ventrolateral geniculate body nuclei and the hypothalamic suprachiasmatic nuclei. Finally, the raphe medial tract receives fibers from both the median and dorsal raphe nuclei and runs ventrally between the fasciculus retroflexus and projects to the interpeduncular nucleus and the midline mammillary body. Further studies were done to test whether the fiber tracts travelling in the MFB contained 5-HT. Unilateral (left) injections of 5,7-dihydroxytryptamine (5 μgm/400 nl) 18 days before midbrain raphe microinjections of 3H-proline produced a reduction in the grain concentrations in all the ascending fibers within the MFB. Furthermore, pharmacological and behavioural evidence was obtained to show that the 5-HT system had been unilaterally damaged; these animals displayed preferential ipsilateral turning in a rotameter which was strongly reversed to contralateral turning after 5-hydroxytryptophan administration. The results show that DR and MR nuclei have numerous ascending projections whose axons contain the transmitter 5-HT. The results agree with the neuroanatomical distribution of the 5-HT system previously determined biochemically, histochemically, and neurophysiologically. The midbrain serotonin system seems to be organized by a series of fiber pathways. The fast transport rate in these fibers was found to be about 108 mm/day.

Direct and indirect preoculomotor pathways of the brainstem: An autoradiographic study of the pontine reticular formation in the cat

Article

Sep 1977
J COMP NEUROL

Ann M Graybiel

The efferent connections of the paramedian pontine reticular formation have been studied in the cat in autoradiographic experiments designed to analyze direct and indirect preoculomotor pathways. Injections of tritium-labelled amino acids were placed (1) near the border between the oral and caudal subdivisions of the nucleus pontis centralis, (2) in more rostral and dorsal parts of the pontine tegmentum, (3) at the pontomesencephalic border, and (4) at the pontomedullary border. Tegmental injections of the first group were unique in labelling a direct ipsilateral pathway to the abducens nucleus and nucleus prepositus hypoglossi. More rostral injections failed to produce discrete labelling of the nuclei of the extraocular muscles but labelled nearby tegmentum and central gray substance. Caudal deposits, involving the pontomedullary reticular formation at its junction with the abducens, perihypoglossal and vestibular nuclei, labelled a decussating fiber system reaching the contralateral abducens nucleus, nucleus prepositus hypoglossi and parts of the vestibular complex. In a single additional case, an injection placed in the oculomotor complex produced heavy labelling of the abducens nuclei. All tegmental injections labelled discrete reticulo-reticular and other variably complex longitudinal pathways. Most injections of (a) the pontomedullary and (b) the pontomesencephalic zones elicited labelling of the pretectum including the nucleus of the optic tract. An incidental finding in the latter group was dense labelling of the pars compacta of the substantia nigra, subthalamic nucleus, and (1 case) entopeduncular nucleus; in one case of each of these groups, labelled fibers were traced to the external pallidum. These observations suggest that, with respect to its efferent oculomotor affiliations, the paramedian pontine tegmentum may be divided into compartments whose supranuclear connections are distinct but for the most part heavily weighted toward influencing the abducens nucleus and periabducens region. Considered within the framework of behavioral and physiological studies of the so-called pontine gaze center, and studies of pontine afferents, the findings are interpreted as suggesting a functional differentiation of these tegmental zones with respect to their influence on eye-head coordination.

Regional Distribution of Circulating Blood During Submersion Asphyxia in the Duck

Article

Sep 1964
Acta Physiol Scand

Kjell Johansen

Regional blood flow distribution in ducks was estimated from fractional distribution of Rb86CI. A comparison was made between normally breathing ducks and submerged ducks. The data document that conspicuous changes in regional blood flow take place upon submersion. The skin, skeletal muscle, and organs of the gastrointestinal system showed a marked decrease in activity in the submerged condition down to an average of 3.9 % for the gizzard, 29.4 % for skin excised from the thorax and 11.0 % for gastrocnemius muscle. Surprising exceptions to this were displayed by tissues in the cranial part of the animals. Thus both skin and muscle from the head region showed an increase in activity during submersion. The same was true for the excised eye. The esophagus similarly showed an increased activity in the submerged animals. The myocardium from both atria and ventricles showed a striking increase amounting to 4.1 times higher activity in the left ventricular myocardium in the submerged animals. The change in vasomotor constrictor tone taking place upon submersion is thus highly selective and possibly segmentally oriented giving an increase in peripheral resistance to most organs posterior to the heart while the most cranial tissues seem to be subjected to a general decrease in vasoconstrictor tone with an increased blood flow. Activity in the kidneys was markedly consistent and 9.1 % of the value found in normally breathing animals. The adrenals showed an interesting increase in activity on the average as high as 4.9 times the value in normally breathing animals.

Afferent Connections of the Habenular Nuclei in the Rat. A Horseradish Peroxidase Study, with a Note on the Fiber-of-Passage Problem

Article

May 1977
J COMP NEUROL

The afferent connections of the habenular complex in the rat were examined by injecting horseradish peroxidase (HRP) into discrete portions of the habenular nuclei by microelectrophoresis. 1. HRP deposits confined to the lateral half of the lateral habenular nucleus labeled a multitude of cells in the entopeduncular nucleus. Numerous labeled cells also appeared in such cases in the lateral hypothalamus, indicating that the lateral habenular nucleus is a major convergence point of projections from these otherwise. 2. HRP injected into the medial part of the lateral habenular nucleus labeled cells in the same regions, but more in the diagonal band and fewer in the entopeduncular nucleus than were labeled by more lateral injections. The contrast suggests that the projections from the basal forebrain and entopeduncular nucleus to the lateral habenular nucleus are somewhat topographically organized. 3. Injections of the medial habenular nucleus labeled an abundance of cells in the posterior parts of the supracommissural septum, but also a small number of cells in the diagonal band and mesencephalic raphe. 4. HRP injected into the stria medullaris labeled cells in all of the afore-mentioned areas and, in addition, cells in several olfactory structures, confirming that HRP may be taken up by fibers of passage and label their cells of origin, and suggesting that olfactory structures contribute fibers to the stria medullaris that do not terminate in the habenula.

Cell bodies of origin of reticular projections from the superior colliculus in the cat: An experimental study with the use of horseradish peroxidase as a tracer

Article

Nov 1978
J COMP NEUROL

By use of the retrograde axonal transport of horseradish peroxidase (HRP), the projection from the superior colliculus (SC) to the brain stem reticular formation (RF) was investigated in the cat. A 0.2–0.5 μl of a 50% suspension of Sigma VI HRP was injected stereotactically in various portions of the pontomedullary RF, and, as a control to the injection to the RF, in the inferior olive or in the spinal cord. Labeled cells were found within and deep to the intermediate gray layer of the SC in the cats which survived for two or three days after HRP injection. The number of the labeled cells varied, according to the difference in the site of injection and the amount of injected HRP. About 400 labeled cells in twenty 50-μm sections, taken every fifth of the SC, occurred throughout its rostrocaudal extent, particularly in the case where the medial portion of the border zone of the nucleus reticularis pontis oralis and the caudalis (R.p.o.-R.p.c. zone) or the border zone of the nucleus reticularis pontis caudalis and the gigantocellularis (R.p.c.-R.gc. zone) was heavily stained after three days of survival period. From 10 to 15% of these labeled cells were large in size (more than 40 μm in diameter), 20–30% were medium sized and the rest (60–70%) were small (10–25 μm). On the other hand, when HRP was placed in the inferior olive only eight cells were labeled in the SC, seven of which were small and medium sized. When HRP was injected in the gray matter of C1C3 level of the spinal cord, a total of 70 tectal cells (14, 42, and 14 were large, medium, and small cells, respectively) were observed to be labeled. The findings of the tectoreticular neurons are discussed and compared with those of the tectoolivary and the tectospinal neurons. Thus the three kinds of tectal neurons are located within and deep to the intermediate gray layer. The number of the labeled cells and the percentage of the collicular neurons of different sizes are obviously different among the three different projections. Topographic correlations between the SC and the RF could not be discerned in the present materials. These results were discussed in relation to possible influences of the tectoreticular neurons upon the extraocular and the spinal motoneurons.

Efferent connections of the centromedian and parafascicular thalamic nuclei: An autoradiographic investigation in the cat

Article

May 1985
J COMP NEUROL

The efferent projections of the centromedian and parafascicular (CM-Pf) thalamic nuclear complex were analyzed by the autoradiographic method. Our findings show that the CM-Pf complex projects in a topographic manner to specific regions of the rostral cortex. These fibers distribute primarily to cortical layers I and III; however, the projection to layer I is more extensive. Following an injection into the rostral portion of the CM-Pf complex, label is found within the lateral rostral cortex, particularly within the presylvian, anterior ectosylvian, and anterior lateral sulci, and within the rostral medial cortex where label is present within the cruciate and anterior splenial sulci and anterior cingulate gyrus. An injection into the caudal dorsal portion of the CM-Pf complex results in label within the more ventral portions of the rostral lateral cortex where it is present within the anterior sylvian gyrus, presylvian regions, and gyrus proreus; and within the rostral medial cortex, where it is present within the rostral cingulate gyrus, and within the cruciate sulcus, and an extensive region ventral to the cruciate sulcus which includes the anterior limbic area. Injections into the caudal ventral portion of the CM-Pf complex result in virtually no cortical label, although a few labeled fibers are found in the subcortical white matter. The subcortical projection from the CM-Pf complex terminates within the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, zona incerta, fields of Forel, hypothalamus, thalamic reticular nucleus, and rostral intralaminar nuclei. Prominent silver grain aggregates are also present within the ventral lateral, ventral anterior, ventral medial, and lateral posterior nuclei, and ventrobasal complex. The aggregates in the thalamus appear to be fibers of passage, but whether these are also terminals cannot be determined with the techniques used in the present study.

Nucleus tegmenti pedunculopontinus: Efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase

Article

Dec 1983
NEUROSCIENCE

The efferent connections of the brain stem nucleus tegmenti pedunculopontinus were studied in the rat using the techniques of anterograde and retrograde transport of the enzyme horseradish peroxidase, laying particular emphasis on that part of pedunculopontinus which receives direct descending projections from the basal ganglia and related nuclei. In a preliminary series of experiments horseradish peroxidase was injected into either the entopeduncular nucleus or the subthalamic nucleus and, following anterograde transport of enzyme, terminal labelling was identified in nucleus tegmenti pedunculopontinus, surrounding the brachium conjunctivum in the caudal mesencephalon.

Distribution of serotonin-immunoreactivity in the central nervous system of the rat—Cell bodies and terminals

Article

Feb 1981
NEUROSCIENCE

Harry W M Steinbusch

The localization and distribution of serotonin (5-hydroxytryptamine, 5-HT) has been studied with the indirect immunofluorescence technique using a highly specific and well-characterized antibody to 5-HT. In neuron systems 5-HT was found to be primarily present with a distribution similar to that observed in basic mappings carried out with the formaldehyde-induced fluorescence method. In addition to the nine areas originally described, several other areas in the mesencephalon and rhombencephalon appeared to contain widely distributed 5-HT-positive perikarya. In the median eminence 5-HT fluorescent mast cells could be visualized. No 5-HT-positive nerve cell bodies could be observed either in the telencephalon or diencephalon.

Direct projections from the anterior pretectal nucleus to the dorsal accessory olive in the cat: an anterograde and retrograde WGA-HRP study

Article

Sep 1983
BRAIN RES

Direct projections from the anterior pretectal nucleus (APN) to the dorsal accessory olive (DAO) were found in the cat by the anterograde and retrograde WGA-HRP methods. The dorsal or the ventral portions of the rostral half of the APN pars compacta send fibers respectively to the lateral or the medial portions of the whole rostrocaudal extent of the DAO. These APN-DAO fibers can be considered to play roles in some somatomotor mechanisms.

Retrograde axonal transport and the demonstration of non-specific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey

Article

Apr 1974

The intralaminar nuclei of the thalamus have been examined particularly in the rat but with additional observations in the cat and squirrel monkey, with a view to determining the extent of their connections with the cerebral cortex and/or striatum. Cells in the intralaminar and other thalamic nuclei were labeled by retrograde axonal transport of the enzyme, horseradish peroxidase, from injection sites of varying size in the cerebral cortex and striatum. This system provides a useful means of determining certain parameters of the horseradish peroxidase technique. It is concluded that the degree of retrograde labeling of a cell is primarily dependent upon the number and concentration of its axon terminals in the vicinity of the injection site. Injections of the striatum in the rat and monkey cause intense labeling of many cells in the intralaminar nuclei. Conversely, injections in the medial, frontal and parietal cortex of all three species, though leading to heavy labeling of many cells in the appropriate thalamic relay nuclei, result in only light labeling of relatively few cells in the intralaminar nuclei. Cells in a single intralaminar nucleus, however, though showing a broad topographical relationship, can be labeled from quite wide areas of the cerebral cortex. These results are consistent with the view that the intralaminar nuclei (including the parafascicular and centre médian) project densely to the striatum and sparsely and diffusely upon the cerebral cortex.

The cortical projection of the thalamic intralaminar nuclei restudied by means of the HRP retrograde transport

Article

Apr 1977
NEUROSCI LETT

Following multiple injections of HRP in different cortical areas in the cat, labeled cells were, in some cases, found in the thalamic intralaminar nuclei. The following cortical zones were found to constitute the preferential target for the projections from the respective intralaminar nuclei: motor and anterior suprasylvian areas for the nucleus centralis lateralis, cingulate cortex for the nuclei paracentralis and centralis medialis, sensory and motor areas for the nucleus centrum medianum. These data are compared with the results previously obtained by means of the retrograde degeneration technique.

Multiple sources of thalamic input to the primate motor cortex

Article

Jun 1975
BRAIN RES

Peter Leonard Strick

Hippocampal innervation by serotonin neurons of the mibrain raphe in the rat

Article

Nov 1975

The organization of the brainstem serotonin neuron projection to the hippocampal formation was analyzed in the rat. This projection arises in the raphe nuclei of the midbrain. Following destruction of the midbrain raphe nuclei, chiefly nucleus centralis superior, there is a 72% decrease in hippocampal serotonin content. Injection of tritiated amino acid into the midbrain raphe nuclei results in transport of tritiated protein to the hippocampal formation and this transport is blocked in animals pretreated by intraventricular administration of 5,6-dihydroxytryptamine (5,6-DHT). Autoradiographic analysis indicates that the transport reaches the hippocampal formation primarily via two major pathways, the cingulum and the fornix. Cingulum fibers terminate predominantly in the dorsal hippocampus whereas the fornix distributes throughout the entire hippocampal formation. Some fibers reach the ventral hippocampus from the entorhinal area. Within the hippocampus there is dense labeling in a restricted lamina of the CA1 stratum lacunosum-moleculare with moderate labeling in stratum radiatum. Stratum oriens is sparsely labeled in CA1 and moderately so in CA2 and CA3. Stratum radiatum and stratum lacunosum-moleculare are moderately densely labeled in CA2 and Ca3. The area dentata is sparsely to moderately labeled in the molecular layer and heavily labeled in a thin lamina of the hilar zone immediately beneath the granule cell layer. The remaining hilar zone is moderately labeled. All of the discrete labeling of the hippocampus and area dentata described above is absent in animals pretreated with 5,6-DHT. These observations indicate that serotonin neurons of the midbrain raphe provide a highly organized innervation of the hippocampal formation in the rat.

Connections of the pretectum in the cat J

Article

Jul 1977

Nancy E J Berman

The connections of the pretectal complex in the cat have been examined by anatomical methods which utilize the anterograde axonal transport of tritiated proteins or the retrograde axonal transport of the enzyme horseradish peroxidase. Following injections of tritiated amino acids into the eye, label can be seen in the contralateral and ipsilateral nucleus of the optic tract and olivary nucleus where it appears as two or three finger‐like strips. Following large injections of tritiated amino acids into the pretectal complex transported label accumulates ipsilaterally in a region dorsolateral to the red nucleus, the central and pericentral divisions of the tegmental reticular nucleus, the intermediate layers of the superior colliculus, the nucleus of Darkschewitch, the thalamic reticular nucleus, zona incerta and fields of Forel, the central lateral nucleus, the pulvinar nucleus and the ventral lateral geniculate nucleus. Contralaterally label accumulates in the nucleus of the posterior commissure, the interstitial nucleus of Cajal, the anterior, posterior and medial pretectal nuclei, and the ventral lateral geniculate nucleus From smaller injections, more or less well confined to single nuclei, the following patterns of connections are demonstrated. The nucleus of the optic tract projects to the ipsilateral ventral lateral geniculate nucleus and pulvinar nucleus and to the contralateral nucleus of the posterior commissure. The anterior pretectal nucleus projects to the ipsilateral central lateral nucleus, the reticular nucleus, zona incerta, fields of Forel, the region dorsolateral to the red nucleus and to the contralateral anterior pretectal nucleus. The posterior pretectal nucleus seems to project only to the ipsilateral reticular nucleus and zona incerta. The central tegmental fields deep to the pretectum project to the tegmental reticular nucleus of the brainstem. When the injection involves the nucleus of the posterior commissure label is seen in the ipsilateral nucleus of Darkschewitch, and in the contralateral nucleus of the posterior commissure and interstitial nucleus of Cajal but no nucleus of the pretectum could be positively identified as projecting to any of the motor nuclei of cranial nerves III, IV, and VI. Following large injections of horseradish peroxidase into the pretectal complex, labeled cells are seen in the superficial layers of the ipsilateral superior colliculus, in the ipsilateral ventral lateral geniculate nucleus, reticular nucleus and zona incerta and in the contralateral anterior, medial and posterior pretectal nuclei, nucleus of the optic tract and ventral lateral geniculate nucleus.

Mesencephalic and diencephalic afferents to the superior colliculus and periaqueductal gray substance demonstrated by retrograde axonal transport of HRP in the cat

Article

Jun 1978
BRAIN RES

The mesencephalic and diencephalic afferent connections to the superior colliculus and the central gray substance in the cat were examined by means of the retrograde transport of horseradish peroxidase (HRP). After deep collicular injections numerous labeled cells were consistently found in the parabigeminal nucleus, the mesencephalic reticular formation, substantia nigra pars reticulata, the nucleus of posterior commissure, the pretectal area, zona incerta, and the ventral nucleus of the lateral geniculate body. A smaller number of cells was found in the inferior colluculus, the nucleus of the lateral lemniscus, the central gray substance, nucleus reticularis thalami, the anterior hypothalamic area, and, in some cases, in the contralateral superior colliculus, Forel's field, and the ventromedial hypothalamic nucleus. Only the parabigeminal nucleus and the pretectal area showed labeled cells following injections in the superficial layers of the superior colliculus. In the cats submitted to injections in the central gray substance, labeled cells were consistently found in the contralateral superior colliculus, the mesencephalic reticular formation, substantia nigra parts reticulata, zona incerta and various hypothalamic areas, especially the ventromedial nucleus. In some cases, HRP-positive cells were seen in the nucleus of posterior commissure, the pretectal area, Forel's field, and nucleus reticularis thalami. A large injection in the mediodorsal part of the caudal mesencephalic reticular formation, which included the superior colliculus and the central gray substance, resulted in numerous labeled cells in nucleus reticularis thalami. The findings are discussed with respect to the suggested functional division of the superior colliculus into deep and superficial layers. Furthermore, the possible implications of labeled cells in zona incerta and the reticular thalamic nucleus are briefly discussed.

Observations on the orthograde and retrograde transport of horseradish peroxidase in the cat

Article

Feb 1979
J Hirnforsch

Horseradish peroxidase (HRP) was applied to the precruciate cortex of the cat. The peroxidase was either applied directly to the surface or injected by glass micropipettes in single or multiple injections. Retrograde as well orthograde transport was observed by light and electron microscopy in different areas: in the thalamus: the nucleus ventralis lateralis and the nucleus centrum medianum, in the red nucleus and in the spinal cord. The distribution of HRP within the nervous elements of the nuclei: axon terminals and/or perikarya and dendrites, was observed by light and electron microscopy. HRP was present in dendrites and perikarya, indicating retrograde transport, in experiments where damage to the injected nervous tissue could be suspected. However HRP appeared restricted to the nerve endings, indicating orthograde transport, when the damage seemed to be minimal. This effect of injury on retrograde transport of HRP was further confirmed by experiments using bilateral HRP injections and unilateral lesions of the spinal cord to label rubro-spinal cells. Thus retrograde transport of HRP could be induced by lesion in systems where it does not occur normally. The normal intra-axonal transport of HRP appears to be from the perikaryon to the nerve endings. This orthograde transport can be seen under the light microscope and can be confused with faint retrograde labeling.

Oculomotor Afferents in the Monkey Demonstrated With Horseradish Peroxidase

Article

Feb 1979
BRAIN RES

The afferents to the oculomotor nucleus were examined in the macaque monkey by means of horseradish peroxidase. The demonstration of afferents from the contralateral interstitial nucleus of Cajal, and from the nearby rostral interstitial nucleus of the medial longitudinal fasciculus, predominantly ipsilateral to the injection site, confirms the significant role of these two regions as premotor structures. HRP label in the pretectal area was strictly confined to the olivary nucleus and the corresponding pathway seems to concern the Edinger-Westphal nucleus in particular. A purely crossed internuclear pathway emanating from the abducens nucleus could be established, and evidence for the presence of intranuclear connections within the oculomotor complex itself was found. Ipsilateral afferents from the superior vestibular nucleus and bilateral connections from the medial vestibular nucleus and the y-group were prominent. A projection, showing some rostrocaudal organization within the oculomotor nucleus, arises from the ipsilateral perihypoglossal complex, and other afferents originated from the underlying medullary reticular formation. No evidence was found for the existence of afferents from the paramedian pontine reticular formation, the nucleus Darkschewitsch, the nuclei of the posterior commissure, the lateral tegmentum and the dentate nucleus.

Behavioral functions of the reticular formation brain Res

Article

Aug 1979
BRAIN RES

Jerome M. Siegel

Studies of the behavioral correlates of activity in reticular formation cells, usually performed in restrained animals, have found units whose discharge relates to sensory stimuli, pain and escape behavior, conditioning and habituation, arousal, complex motivational states, REM sleep, eye movements, respiration and locomotion. Units with these different behavioral correlates were found in the same anatomical areas. Most studies report that a large proportion of encountered cells related to the behavior being studied. If one adds up the reported percentages, the total far exceeds 100%. Therefore it appears that many investigators are looking at the same cells and reaching very different conclusions about their behavioral roles. On the basis of observations in unrestrained cats, it is hypothesized that discharge in most RF cells is primarily related to the excitation of small groups of muscles. This hypothesis can parsimoniously explain many previous observations on the behavioral correlates of these cells, and is consistent with anatomical, physiological and phylogenetic studies of the reticular formation. The hypothesized simplicity of reticular formation unit function is contrasted with the complexity of the behavioral functions mediated by the RF, and the implications of this contrast discussed.

Thalamo-cortical projections for recruiting responses and spindling-like responses in the parietal cortex

Article

Feb 1975

1. The thalamic neurones sending their axons to the parietal association cortex (middle suprasylvian gyrus) and receiving monosynaptic excitation from the cerebellar (interpositus or lateral) nucleus were recorded with microelectrodes extracellularly and intracellularly around the anterior ventral (VA) nucleus of the thalamus in cats. Such thalamic neurones are known to carry exclusively the impulses responsible for superficial thalamo-cortical (T-C) responses in the parietal cortex, being called superficial T-C neurones (see Sasaki et al., 1972a, b). 2. Repetitive (6–9/sec) stimulation of the centrum medianum-parafascicular complex (CM) or the intralaminar nuclei (IL) of the thalamus elicited grouped spike discharges of the neurone in synchronization with the recruiting responses in the parietal cortex. The grouped discharges usually preceded the respective cortical responses by several milliseconds. Numbers of the spikes in the grouped discharges increased and decreased as the recruiting responses waxed and waned on the repetitive stimulation. 3. The superficial T-C neurones also showed similar grouped discharges in synchronization with spindling-like, surface-negative cortical responses which occurred spontaneously or were evoked by single thalamic stimulation. 4. It was concluded that the superficial T-C neurones can convey impulses for recruiting responses and spindling-like responses from the thalamus directly to the cerebral cortex. They are supposed to constitute the final T-C pathway of the neuronal circuits of the recruiting system, i.e., non-specific T-C projection system.

Beckstead RM, Domesick VB, Nauta WJH. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res 175: 191-217

Article

Nov 1979
BRAIN RES

Small injections of tritiated leucine and proline confined to the ventral tegmental area (AVT) were found to label fibers ascending: (a) to the entire ventromedial half of the striatum, but most massively to the ventral striatal zone that includes the nucleus accumbens; (b) to the thalamus: lateral habenular nucleus, nuclei reuniens and centralis medius, and the most medial zone of the mediodorsal nucleus; (c) to the posterior hypothalamic nucleus and possibly the lateral hypothalamic and preoptic region; (d) to the nuclei amygdalae centralis, lateralis and medialis; (e) to the bed nucleus of the stria terminalis, the nucleus of the diagonal band, and the medial half of the lateral septal nucleus; (f) to the anteromedial (frontocingulate) cortex; and (g) to the entorhinal area. Further AVT afferents descend to the medial half of the midbrain tegmentum including an anterior region of the median raphe nucleus, to the ventral half of the central grey substance including the dorsal raphe nucleus, to the parabrachial nuclei, and to the locus coeruleus.

Heterogeneous afferents to the inferior parietal lobule of the Rhesus monkey revealed by the retrograde transport method

Article

Apr 1977
BRAIN RES

The sources of afferent connections to the inferior parietal lobule (rostral part of the area 7 of Brodman; PF and rostral part of PG of von Bonin and Bailey) were examined with the retrograde transport method in infant and adult rhesus monkeys. Two to 3 days after injections of horseradish peroxidase (HRP) into the cortex, the animals were anesthetized, and the brains fixed and processed for the histochemical demonstration of the enzyme marker. Labeled neurons were found in layer III in the ipsilateral prefrontal, parietal, occipital and temporal cortices, notably in areas 5, 19, 22 and 46 of Brodmann, and in area 7 of the contralateral parietal cortex. In the thalamus, HRP-positive cells were located ipsilaterally in the medial pulvinar nucleus in the nuclei centrum medianum and parafascicularis, as well as in the rostral thalamus, lateral and medial to the mammillothalamic tract, in the nucleus ventralis anterior and nucleus paracentralis. Numerous labeled cells were also identified in the magnocellular nuclei of the basal forebrain, in the dorsal and medial raphe nuclei, and in the locus coeruleus. Most of the cells in these regions were located in the hemisphere ipsilateral to the injections, but a number of them were also found in the contralateral hemispher. In adult monkeys, brownish granules in the cytoplasm of some cells were interpreted as endogenous pigment or due to various pigment precursors. However, all 14 locations listed above were identified in the infant monkey in which endogenous pigment was not a confounding factor.

Descending pathways from the superior colliculus: An autoradiographic analysis in the rhesus monkey (Macaca mulatta)

Article

Jun 1977

John K. Harting

The autoradiographic tracing method has been used to identify the various descending tectofugal pathways and their targets in the rhesus monkey (Macaca mulatta). The present data reveal that the majority of descending tectofugal axons arise from collicular laminae which lie ventral to the stratum opticum (layer 3). Such descending axons can be grouped into two major bundles or tracts, i.e., the ipsilateral tectopontine-tectobulbar tract and the crossed tectospinal tract (or the predorsal bundle). There is, in addition to these two major pathways, a smaller, commissural projection. The ipsilateral pathway courses laterally and ventrocaudally to terminate within the parabigeminal nucleus, the mesencephalic reticular formation, the dorsal lateral pontine gray (in several discrete patches), the dorsal lateral wing of the nucleus reticularis tegmenti pontis, and within the nucleus reticularis pontis oralis. Other ipsilateral targets of the deep tectal layers are the cuneiform nucleus and the external nucleus of the inferior colliculus. In several experiments transported protein is also apparent within the substantia nigra. Axons which comprise the tectospinal tract, or the predorsal bundle, cross within the dorsal tegmental decussation and descend within the brainstem in a position slightly lateral to the midline. The most rostral and quite extensive target of the predorsal bundle is the nucleus reticularis tegmenti pontis. As the predorsal bundle courses caudally within the pontine tegmentum, labeled axons enter the dorsal and medial regions of both the oral and the caudal divisions of the nucleus reticularis pontis. At caudal medullary levels, the majority of the labeled axons comprising the predorsal bundle pass ventrally to end quite profusely within the subnucleus b of the medial accessory nucleus of the inferior olivary complex. Caudal to this only a few scattered, labeled axons can be followed into the cervical spinal cord. Labeled axons also pass to the opposite, or contralateral colliculus via the tectal commissure. Such axons appear to arise and end primarily within the deeper tectal layers. In one experiment, the injection invaded the mesencephalic nucleus of the trigeminal nerve. Labeled axons were apparent within the motor nucleus, the chief sensory nucleus (quite profusely) and within the spinal or descending nucleus of the trigeminal nerve.

The efferent connections of the nucleus raphe centralis superior in the rat as revealed by autoradiography. Brain Res 166: 1-8

Article

May 1979
BRAIN RES

By chronically implanting a glass micropipette filled with tritiated leucine in the raphe centralis superior of the rat, the projection of this nucleus was traced by radioautography. The majority of the ascending projections were located within the ventral tegmental area and, further rostrally, the median forebrain bundle. Along the course of this bundle numerous fibers branched successively into the mammillary peduncle, the fasciculus retroflexus, the stria medullaris, the fornix and the cingulum. The most significant projections included the ones to the interpeduncular nucleus, the mammillary bodies, the habenular nuclei and the hippocampus. No projections were detected in the striatum, the cortex piriformis or the amygdala. Descending projections diffused to the pontine reticular formation and central gray through the medial and the dorsal longitudinal bundles. In addition widespread projections were also seen in nuclei located near the raphe centralis superior: raphe nuclei, dorsal and ventral tegmental nuclei.

Three bulbospinal pathways from the rostral medulla of the cat: An autoradiographic study of pain modulating systems

Article

Mar 1978

Small amounts of 3H-leucine were injected into discrete regions in the rostral medulla of the cat. Descending projections from these sites were studied with autoradiographic methods. On the basis of differential projections to the medulla and spinal cord, three distinct regions were delineated. Nucleus reticularis gigantocellularis (Rgc), located dorsally in the medullary reticular formation, projects primarily to “motor” related sites, including cranial motor nuclei VI, VII, XII, nucleus intercalatus, and a part of the ipsilateral medial accessory olive. The projection to the spinal cord is primarily via the ipsilateral ventrolateral and contralateral ventral funiculi. The Rgc terminal field is in lamina VII and VIII ipsilateral and lamina VIII contralateral to the injection site. In contrast, nucleus raphe magnus, (NRM) located ventrally, in the midline of the rostral medulla projects primarily to structures with known nociceptive and/or visceral afferent input. These sites include the solitary nucleus, the dorsal motor nucleus (X) and the marginal and gelatinous layers of the spinal trigeminal nucleus caudalis. The projection to the spinal cord is bilateral, via the dorsolateral funiculus. Terminal fields are found in the marginal zone and the substantia gelatinosa of the dorsal horn, and more deeply in lamina V, medial VI and VII. Nucleus reticularis magnocellularis (Rmc), located lateral to NRM and ventral to Rgc, has an overlapping projection with NRM, but the projection is ipsilateral. This difference between Rmc and Rgc is correlated with cytoarchitectural features of the two regions. The possibility that the raphe-spinal pathway in the DLF mediates opiate and brain stimulation-produced analgesia is discussed.

Superior colliculus connections with the extraocular motor nuclei in the cat

Article

May 1978

Direct and indirect projections from the cat superior colliculus to the extraocular motor nuclei were studied using the orthograde autoradiographic tracing method, the retrograde horseradish peroxidase technique, and Golgi methods. The results show that the superior colliculus projects to the central gray matter directly overlying the oculomotor complex. This projection arises almost entirely from the rostral third of the colliculus, and it terminates most heavily over the rostral half of the oculomotor complex. Dendrites of oculomotor cells extend into this tectal termination zone, making direct tecto-oculomotor contacts possible. Central gray cells within this termination zone project bilaterally to the abducens nuclei. It is proposed that the superior colliculus projection to the supraoculomotor central gray matter and the projection from the central gray matter to the abducens nuclei play a role in convergent eye movements. The superior colliculus projects lightly to a cell group directly ventrolateral to the trochlear nucleus. The superior colliculus sends a small direct projection to the contralateral abducenns nucleus and a substantial projection to wide regions of the reticular formation that have been shown previously to project, in turn, to the abducens nucleus. Colliculus cells projecting to the abducens nucleus and adjacent reticular formation are located only in the caudal three-fourths of the colliculus, where they become increasingly concentrated at successively more caudal levels. It is proposed that the graded density of the cells of origin of this projection is the basic structural mechanism by the which the colliculus generates horizontal foveating saccades of different amplitudes. Laminar analysis of the origin of all the superior colliculus projections to the extraocular motor regions described here revealed that they arise mostly from the stratum griseum intermedium.

Somatic sensory projections to the pretectum in the cat

Article

Jan 1979
BRAIN RES

Distribution of thalamo-caudate neurons in the cat as demonstrated by horseradish peroxidase

Article

Feb 1979

Distribution of thalamocaudate neurons in the cat was examined by means of the horseradish peroxidase (HRP) method. After injection of HRP into the head of the caudate nucleus (Cd), thalamic neurons labeled with HRP were observed mainly in the rhomboid nucleus (Rh), central medial nucleus (Ce), centre médian-parafascicular complex (CM-Pf) as well as in the midline and intralaminar regions surrounding the mediodorsal nucleus (MD). Distribution of HRP-labeled neurons in the centrolateral nucleus (CL) were localized in the medial parts of the nucleus. Many HRP-labeled neurons were also seen in the substantia nigra (SN) and retrorubral nucleus (Rr). Additionally, HRP-labeled neurons were found in the ventrolateral portions of the anteromedial nucleus (AM), lateral portions of the MD, ventral tegmental area of Tsai (vT) and the midline raphe nuclei, such as the rostral lineal (rL), central lineal (cL) and dorsal raphe (dR) nuclei.

Sources of Subcortical Projections to the Superior Colliculus in the Cat

Article

Mar 1979

A comprehensive search for subcortical projections to the cat superior colliculus was conducted using the retrograde horseradish peroxidase (HRP) method. Over 40 different subcortical structures project to the superior colliculus. The more notable among these are grouped under the following categories. Visual structures : ventral lateral geniculate nucleus, parabigeminal nucleus, pretectal area (nucleus of the optic tract, posterior pretectal nucleus, nuclei of the posterior commissure). Auditory structures : inferior colliculus (external and pericentral nuclei), dorsomedial periolivary nucleus, nuclei of the trapezoid body, ventral nucleus of the lateral lemniscus. Somatosensory structures : sensory trigeminal complex (all divisions, but mainly the γ division of nucleus oralis), dorsal column nuclei (mostly cuneate nucleus), and the lateral cervical nucleus. Catecholamine nuclei : locus coeruleus, raphe dorsalis, and the parabrachial nuclei. Cerebellum : medial, interposed, and lateral nuclei, and the perihypoglossal nuclei. Reticular areas : zona incerta, substantia nigra, midbrain tegmentum, nucleus paragigantocellularis lateralis, and the hypothalamus. Evidence is presented that only the parabigeminal nucleus, the nucleus of the optic tract, and the posterior pretectal nucleus project to the superficial collicular layers ( striatum griseum superficiale and stratum opticum ), while all other afferents terminate in the deeper layers of the colliculus. Also presented is information concerning the rostrocaudal distribution of some of these afferent connections. These findings stress the multiplicity and diversity of inputs to the deeper collicular layers, and more specifically, identify multiple sources of the physiologically well‐known representations of the somatic and auditory modalities in the colliculus.

An autoradiographic study of the pathways from the pontine reticular formation involved in eye movements

Article

Jun 1976
BRAIN RES

The raphe nuclei of the cat brain stem: A topographical atlas of their efferent projections as revealed by autoradiography

Article

Oct 1976
BRAIN RES

Stereotaxic injections of [14C]leucine were made in nulei raphe centralis superior, raphe dorsalis, raphe magnus and raphe pontis of the cat. The organization of the regional connections was outlined in a stereotaxic atlas using the autoradiographic tracing method: the majority of the ascending pathways from the rostral raphe nuclei are directed mainly through a ventrolateral bundle via the ventral tegmental area of Tsai, with some lateral extensions to the substantia nigra, and then through the fields of Forel and the zona incerta. More rostrally the fibers are joined to the medial forebrain bundle through the hypothalamic region up to the preoptic area or the diagonal band of Broca. Multiple divisions leave this tract towards the epithalamic or the intralaminar thalamic nuclei, the stria terminalis, the septum, the capsula interna and the ansa lenticularis. The bulk of the rostral projections terminates in the frontal lobe, while some labeling is scarcely distributed throughout the rest of the neocortex. The projections of nucleus (n.) raphe centralis superior are specifically associated with the n. interpeduncularis, the mammillary bodies and the hippocampal formation while the n. raphe dorsalis innervates selectively the lateral geniculate bodies, striatus, piriform lobes, olfactory bulb and amygdala. The rest of the ascending fibers form the centrolateral or the dorsal ascending tracts radiating either in the reticular mesencephalic formation or in the periventricular gray matter. On the contrary there are heavy descending projections from n. raphe centralis superior which distribute to the main nuclei of the brain stem, the central gray matter and the cerebellum. The ascending projections form the caudal raphe nuclei are much less dense. They disseminate mainly in the colliculus superior, the pretectum, the nucleus of the posterior commissure, the preoculomotor complex and the intralaminar nuclei of the thalamus. From n. raphe pontis, a dense labeling is selectively localized at the n. paraventricularis hypothalami with some rostral extensions to limbic areas. Diffuse caudal and rostral projections from both nuclei are observed in the mesencephalic, pontobulbar reticular formation and the cerebellum. The main differences come from the specific localization of their descending bulbospinal tracts inside the lateroventral funiculus of the spinal cervical cord.

Direct projections from thalamic intralaminar nuclei to extra-striate visual cortex in the cat traced with Horseradish peroxidase

Article

Jun 1977

Thalamic projections to the visual cortex were investigated using the Horseradish peroxidase tracing technique. Besides confirmation of a distinct origin of thalamic projections to striate and extra-striate visual cortex, afferents of the intralaminar nuclei (ILN) to visual cortex were demonstrated. These projections of ILN were shown to be specific in that they terminate in areas 18, 19 and Clare Bishop but not area 17. The coupling of these intralaminar projections on to the extra-striate visual system is considered with respect ot orientation of gaze.

Autoradiographic studies of the projections of the midbrain reticular formation: Ascending projections of nucleus cuneiformis

Article

Feb 1976

The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident.

The organization of divergent axonal projections from the midbrain raphe nuclei in the rat

Article

Jan 1986

The intranuclear organization of divergently projecting neurons of the midbrain raphe in the rat was studied by using double retrograde axonal tracing. Paired injections of the tracers N-[acetyl-3H] WGA and horseradish peroxidase were made within known projection targets of the midbrain raphe (caudate-putamen, amygdala, hippocampus, substantia nigra, and locus coeruleus). After injections of either tracer in the aforementioned targets, retrograde labeled neurons were found mainly ipsilaterally and within midline portions of the dorsal raphe nucleus, its caudal B6 portion, and within the linear and superior central nuclei of the median raphe complex. There are discrete intranuclear distributions of raphe neurons that project to these forebrain and brainstem sites, and there is an overall rostrocaudal topographic order within the raphe with neurons projecting to the neostriatum, amygdala, and substantia nigra residing most rostrally and neurons projecting to the hippocampus and/or locus coeruleus occupying caudal portions of the B6 and superior central nuclei. Such distributions of projection neurons suggest the existence of an “encephalotopic” intranuclear organization within the raphe; that is, each central nervous system structure that receives midbrain raphe projections has its own unique representation within a topographically distinct portion of one or more of the raphe subgroups. These findings suggest an overall functional organization within the midbrain raphe nuclear complex whereby rostral portions are associated with the basal ganglia and related nuclei, and caudal portions relate to the limbic system. An intermediate representation of amygdala-projecting raphe neurons functionally conjoins the two. Collateralized neurons are found within complex zones of overlap in the topographically organized distributions of raphe neurons projecting to functionally related structures.

Are there connections between the thalamic reticular and the brainstem reticular formation?

Article

Jan 1986

Increasing awareness that the thalamic reticular nucleus (TRN) plays an important role in controlling the output of cortically projecting cells in nuclei of the dorsal thalamus has focused attention on the question of whether there exist ascending projections to the TRN from the mesencephalic or other parts of the brainstem reticular formation (BRF). We have examined this and the related question of whether the neurons of TRN project to the BRF, by anterograde and retrograde tracing experiments with horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin. Injections of tracer were placed stereotaxically in the BRF at various depths and rostrocaudal and mediolateral coordinates, and the TRN and adjacent nuclei were examined in serial coronal sections, using tetramethylbenzidine as the principal chromogen. Retrogradely labelled cell bodies were consistently seen in hypothalamus and zona incerta but never in TRN, suggesting that, in the rat, TRN neurons do not project caudal to the thalamus. After 54 out of 60 injections, no terminal label was detected in any part of the TRN although such label was present in other parts of the thalamus, including the intralaminar nuclei, in the same sections. We therefore conclude that direct projections from the BRF to the TRN must be extremely sparse, and that those effects of BRF stimulation upon thalamocortical transmission that are mediated by the TRN (rather than by direct projections to dorsal thalamic nuclei) probably depend chiefly on indirect polysynaptic pathways.

Afferent projections to the interpeduncular nucleus in the rat, as studied by retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

Article

Jun 1986

We examined the afferent projections to the subnuclei of the interpeduncular nucleus (IPN) in the rat by means of retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). We observed locations of retrogradely labeled cells following injections of WGA-HRP into the IPN, and distributions of anterogradely labeled fibers and terminals within the IPN following injections into the areas that contain cells of origin of afferents. Results of the retrograde and anterograde experiments have clarified the detailed organization of the IPN afferents. A part of the nucleus incertus, located dorsomedial to the dorsal tegmental nucleus, projects to the contralateral half of the rostral subnucleus of the IPN; the pars caudalis of the dorsal tegmental nucleus projects sparsely to the rostral lateral, dorsal lateral, lateral, caudal, and apical subnuclei predominantly contralaterally; the laterodorsal tegmental nucleus, to most of the subnuclei predominantly contralaterally; the ventromedial central gray rostral to the dorsal tegmental nucleus and lateral to the dorsal raphe nucleus projects to the rostral lateral and dorsal lateral subnuclei predominantly contralaterally; the median raphe nucleus, substantially to all subnuclei; the medial habenular nucleus, in a topographic manner, to the rostral, central, and intermediate subnuclei, to the rostral lateral and lateral subnuclei predominantly ipsilaterally, and to the dorsal lateral subnucleus predominantly contralaterally; the supramammillary nucleus and areas around the origin of the mammillothalamic tract and near the third ventricle project sparsely to the ventral part of the rostral subnucleus and to the central, lateral, caudal and apical subnuclei; the nucleus of the diagonal band, sparsely to the rostral, central, dorsal lateral, caudal, and apical subnuclei. These differential projections of the afferents to the subnuclei of the IPN may reflect its complex functions within the limbic midbrain circuit.

Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat

Abstract

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