Fig 6 - uploaded by Barbara E Jones
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Region of the nucleus locus coeruleus similar to that shown in figures 2, 3. The large, darkly-staining cells (arrows) lying medial and ventral to the trigeminal mesencephalic tract are the ones that exhibit specific catecholamine fluorescence in Falck-Hillarp material. Cresyl violet stain, X 130.
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The nucleus locus coeruleus of the cat brain was studied using the Falck-Hillarp fluorescent histochemical method for the demonstration of cellular monoamines. In the cat, as in other mammals, the locus coeruleus is made up of catecholamine-containing neurons. The cell bodies of these neurons are diffusely distributed in the dorsolateral pontine te...
Citations
... However, other members of the Order Rodentia instead have a diffuse collection of NE cells adjacent to the 4 th ventricle (Sweigers et al., 2017); moreover, in some Rodentia species this less compact LC is located ventrolaterally in the pontine periventricular grey matter away from the 4 th ventricle Da Silva et al., 2006;Limacher et al., 2008). On the other hand, species in the Order Carnivora (e.g., cats and dogs), have a diffuse collection of NE cells within the pontine periventricular grey matter (Chu and Bloom, 1974;Ishikawa et al., 1975;Jones and Moore, 1974;Maeda et al., 1973) that are intermingled with serotonin neurons (Léger and Hernandez-Nicaise, 1980;Léger et al., 1979). Other mammals, such as those in the Orders Artiodactyla (e.g., giraffe, onyx, pig, hippo, and deer), Proboscidea (e.g., elephants), Didelphimorphia (e.g., Opossum), Lagomorpha (e.g., rabbit), or Hydracoidea (e.g., rock hyrax) also have NE cells arranged in a diffuse collection (Blessing et al., 1978;Bux et al., 2010;Crutcher et al., 1978;Davimes et al., 2017;Gravett et al., 2009;Maseko et al., 2013), while the Orders Macroscelidea (e.g., elephant shrew) and aquatic cetaceans that evolved from Artiodactyla have a compact LC resembling laboratory rodents (Manger et al., 2003;Pieters et al., 2010). ...
Cognition fluctuates over relatively faster and slower timescales. This is enabled by dynamic interactions among cortical neurons over similarly diverse temporal and spatial scales. Fast and slow cognitive processes, such as reorienting to surprising stimuli or using experience to develop a behavioral strategy, are also sensitive to neuromodulation by the diffusely-projecting brainstem noradrenergic nucleus, Locus Coeruleus. However, while a dynamic, multi-scale cortical ensemble code influences cognition over multiple timescales, it is unknown to what extent LC neuronal activity operates in this regime. An ensemble code within the LC may permit an interface with cortical ensembles allowing noradrenergic modulation of fast and slow cognitive processes. Alternatively, given that LC neurons are thought to spike synchronously, there may be a mismatch between LC and cortical neuronal codes that constrains how the noradrenergic system can influence cognition. We review new evidence that clearly demonstrates cell type-specific ensemble activity within LC occurring over a range of behaviorally-relevant timescales. We also review recent studies demonstrating that sub-sets of LC neurons modulate specific forebrain targets to control behavior. A critical target for future research is to study the temporal dynamics of projection-specific LC ensembles, their interactions with cortical networks, and the relevance of multi-scale coerular-cortical dynamics to behaviors over various timescales.
... The LC is the primary source of NA in the brain [57,58] and the brain receives most of the NA from these neurons [59][60][61][62]. It was already known that under normal condition these REM-OFF neurons cease firing during REMS [63] and they continue firing during REMSD [45]. ...
Rapid eye movement sleep (REMS) is naturally expressed at least in all the mammals, including humans, studied so far. It is regulated by interplay among complex neuronal circuitry in the brain involving various neurotransmitters. Although the precise function and role of REMS is yet to be deciphered, loss of REMS increases brain excitability; however, the mechanism of action was unknown. As Na-K ATPase is the key molecule that maintains ionic homeostasis across neuronal membrane and modulates the excitability status of neurons, we proposed that REMS deprivation (REMSD) could affect the neuronal Na-K ATPase activity. On the other hand, evidences suggest that REMSD would elevate noradrenaline (NA) level in the brain and it has been proposed that REMS maintains brain NA at an optimum level. Therefore, while attempting to understand and explain the mechanism of action we hypothesized that REMSD-induced elevated NA could modulate Na-K ATPase activity in the brain and thus modulates the neuronal and brain excitability. In this chapter first we discuss the mechanism of increase in NA level in the brain after REMSD. Then we discuss the effect of such elevated NA on neuronal and glial Na-K ATPase activity. We observed that REMSD-induced increase in NA affected neuronal and glial Na-K ATPase activities in opposite manner, while it increased neuronal Na-K ATPase, and it decreased the same in glia. An intricate regulation of Na-K ATPase activity in neurons and glia is likely to be responsible for maintenance of ionic homeostasis in the brain during normal situation, which when disturbed including upon REMS loss patho-physiological changes and symptoms are expressed.
... In cats, depending on size of the neurons and their organization LC has been classified into LC-principal, peri-LC and sub-coeruleus (Sakai et al., 1981). In rats and monkeys, NA-ergic neurons are concentrated at this site; however, in cats, although the core of LC contains NA-ergic neurons, scattered AChergic neurons have also been reported (Aston- Jones and Bloom, 1981;Dahlstrom and Fuxe, 1964;Foote et al., 1983;Jones and Moore, 1974). Further, recent studies show that it possesses GABAergic neurons as well and their role is discussed later. ...
Interactions among REM-ON and REM-OFF neurons form the basic scaffold for rapid eye movement sleep (REMS) regulation; however, precise mechanism of their activation and cessation, respectively, was unclear. Locus coeruleus (LC) noradrenalin (NA)-ergic neurons are REM-OFF type and receive GABA-ergic inputs among others. GABA acts postsynaptically on the NA-ergic REM-OFF neurons in the LC and presynaptically on the latter's projection terminals and modulates NA-release on the REM-ON neurons. Normally during wakefulness and non-REMS continuous release of NA from the REM-OFF neurons, which however, is reduced during the latter phase, inhibits the REM-ON neurons and prevents REMS. At this stage GABA from substantia nigra pars reticulate acting presynaptically on NA-ergic terminals on REM-ON neurons withdraws NA-release causing the REM-ON neurons to escape inhibition and being active, may be even momentarily. A working-model showing neurochemical-map explaining activation of inactivation process, showing contribution of GABA-ergic presynaptic inhibition in withdrawing NA-release and dis-inhibition induced activation of REM-ON neurons, which in turn activates other GABA-ergic neurons and shutting-off REM-OFF neurons for the initiation of REMS-generation has been explained. Our model satisfactorily explains yet unexplained puzzles (i) why normally REMS does not appear during waking, rather, appears following non-REMS; (ii) why cessation of LC-NA-ergic-REM-OFF neurons is essential for REMS-generation; (iii) factor(s) which does not allow cessation of REM-OFF neurons causes REMS-loss; (iv) the association of changes in levels of GABA and NA in the brain during REMS and its deprivation and associated symptoms; v) why often dreams are associated with REMS.
... An important structure in the dorsolateral tegmentum of the pons is LC. It consists of predominantly norepinephrine (NE)-ergic neurons (Foote et al 1983; Jones and Moore 1974). The LC was so named by Wenzels in 1811 because of the dark bluish colouration it exhibited in man and primates (Chu and Bloom 1974). ...
Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified in its present characteristic form about half a century ago, the mechanics of how REM is generated, and what happens upon its loss are not known. Nevertheless, extensive research has shown that norepinephrine plays a crucial role in its regulation. The present knowledge that has been reviewed in this manuscript suggests that neurons in the brain stem are responsible for controlling this state and presence of excess norepinephrine in the brain does not allow its generation. Furthermore, REM sleep loss increases levels of norepinephrine in the brain that affects several factors including an increase in Na-K ATPase activity. It has been argued that such increased norepinephrine is ultimately responsible for REM sleep deprivation, associated disturbances in at least some of the physiological conditions leading to alteration in behavioural expression and settling into pathological conditions.
... The dorsolateral pontine tegmentum of mammals is characterized by the presence of a large population of catecholaminergic neurons (Dahlstrom and Fuxe, 1964;Fuxe et al., 1970;Holets et at., 1988;Jones and Moore. 1974;Jones and Friedman, 1983;Leger et al., 1983;Stevens et al., 1982;Wiklund et al., 1981). In cats, this catecholaminergic neuronal population, estimated at about 9000 cells unilaterally (Wiklund et al., 1981), is scattered over a large area of the dorsolateral pons, namely, in the nuclei locus coeruleus (LC), subcoeruleus (SC), parabrachia ...
Previous studies have revealed the presence of pontospinal neurons with either methionine-enkephalin- or tyrosine hydroxylase-like immunoreactivity in the dorsolateral pontine tegmentum of the cat. Using a combined fast blue retrograde transport technique and simultaneous immunofluorescence histochemistry, the present study was designed to reveal the coexistence of enkephalin and tyrosine hydroxylase in cat coerulospinal neurons and to determine if and to what extent the coerulospinal pathway is heterogeneous. Fast blue-labelled neurons with tyrosine hydroxylase- and enkephalin-like immunoreactivities were found in the nucleus locus coeruleus, nucleus subcoeruleus, Kölliker-Fuse nucleus, and the medial and lateral parabrachial nuclei. Approximately 87% of tyrosine hydroxylase-like immunoreactive neurons had enkephalin-like immunoreactivity, whereas about 76% of the enkephalin-like immunoreactive neurons had tyrosine hydroxylase-like immunoreactivity. About 71% of all coerulospinal neurons exhibited both tyrosine hydroxylase- and enkephalin-like immunoreactivities. These findings indicate that coerulospinal activity may lead to spinal cord effects reflecting both norepinephrine and enkephalin activity in most cases but do not rule out each transmitter's isolated functions.
... Differing from that in the rat brain, the distribution of noradrenergic neurons in the cat brain was found to encompass a broad area of the dorsolateral pontine tegmentum ( Fig. 1; Pin et al., 1968;Jones, 1969;Maeda et al., 1973;Jones and Moore, 1974). The LC complex, which would correspond to both the principal LC and the subcoeruleus nuclei (including pars alpha, dorsal and ventral) in the rat, includes noradrenergic neurons dispersed within the periventricular gray and through the parabrachial nuclei (Jones and Moore, 1974). ...
... Differing from that in the rat brain, the distribution of noradrenergic neurons in the cat brain was found to encompass a broad area of the dorsolateral pontine tegmentum ( Fig. 1; Pin et al., 1968;Jones, 1969;Maeda et al., 1973;Jones and Moore, 1974). The LC complex, which would correspond to both the principal LC and the subcoeruleus nuclei (including pars alpha, dorsal and ventral) in the rat, includes noradrenergic neurons dispersed within the periventricular gray and through the parabrachial nuclei (Jones and Moore, 1974). These cells are most numerous and concentrated in the caudal pons, but also extend rostrally into the oral pons to the level of the isthmus. ...
Despite early suppositions that the noradrenergic (NA) locus coeruleus (LC) neurons play a critical role in the generation and tonic maintenance of wakefulness and paradoxical sleep, further studies indicated that these cells play a nonessential modulatory role in the regulation of these states. Thus, based upon evidence from pharmacological, lesion and single-unit recording studies, it now appears that NA neurons may be important for enhanced periods of attention or stress during wakefulness, though they are not necessary for the tonic maintenance of cortical activation or behavioral arousal during the state. From similar examinations, it has been found that the cessation of activity of NA LC neurons may normally be important in permitting the occurrence of the state of paradoxical sleep. Neighboring cholinergic neurons of the pontomesencephalic tegmentum may also be active during waking and play a role in facilitating thalamocortical activity and transmission, like NA neurons during that state. However, unlike the NA neurons, the cholinergic neurons play an active and essential role in the generation of the state of paradoxical sleep. Generation of the state of paradoxical sleep may depend upon the simultaneous activation of cholinergic neurons and cessation of NA LC neurons, that could be brought about by the intermediary action of local GABA neurons.
... The placement of stimulation electrodes in the present study, distributed within the stereotaxic coordinates of P2 to 3, L2 [41]. Previously, we [21,22] as well as others [9,33,34,42,43,47,50,51,64,68] have demonstrated that these LC sites in the cat contain scattered aggregates of fluorescent catecholaminergic neurons. With their positive immunoreactivity toward the dopamine-fl-hydroxylase enzyme, these cells were regarded as noradrenergic [48], since phenylethanolamine N-methyltransferase-containing cell bodies were absent in the LC region. ...
The locus coeruleus's (LC's) effect on recurrent inhibition of gastrocnemius-soleus (GS) and common peroneal (CP) monosynaptic reflexes (MSRs) was demonstrated to exceed the concomitant facilitation, indicating the independency of LC's disinhibition and facilitation measures in this study. In contrast, the disinhibition effect correlated closely with the recurrently inhibited MSRs. The disinhibition phenomenon was also accompanied by progressive delay and diminution in the Renshaw cell field potential. Hence, the recovery of recurrently inhibited MSRs was probably due, in part at least, to the LC's inhibition of the related Renshaw cell activity. Furthermore, the site-specific, discordant changes in the disinhibition of GS, compared with CP MSRs, as revealed by tracking studies imply that representations of these antagonistic motonuclei may occupy different LC loci. Accordingly, the nonuniform disinhibition may be due to the activation of discrete aggregates of LC neurons which are responsible predominantly in controlling the recurrent inhibitory pathway belonging to one or the other of the antagonistic motonuclei. These findings support a differential LC inhibitory control of Renshaw cell activity, releasing the related motoneurones for the Ia synaptic transmission - a disinhibitory process that is crucial for the LC's independent control of the recurrent circuit of antagonistics extensor and flexor motoneurons.
... Various stressors increase biochemical indices of central norepinephrine (NE) utilization in extensive areas of the rat brain (e.g., Stone, 1975; Tsuda et al., 1982; Anisman et al., 1984). The locus coeruleus (LC), which contains as many as half of all NE neurons in the brain (Chu and Bloom, 1974; Jones and Moore, 1974; Wiklund et al., 198 l), has been hypothesized to play an important role in this response (Korf et al., 1973; Cassens et al., 1980; Glavin, 1985; Weiss and Simson, 1985). Brain areas that receive their sole NE innervation from the LC show these changes during stress (Korf et al., 1973). ...
The present experiment was designed to explore the stress-relatedness of activity in noradrenergic neurons of the locus coeruleus (LC) of behaving cats. A stressor was defined as a stimulus that elicited a significant sympathoadrenal activation as measured by plasma norepinephrine level and heart rate. According to this definition, exposure to 15 min of 100 dB white noise or 15 min of restraint was stressful in cats. In contrast, exposure to inaccessible rats for 15 min was behaviorally activating but nonstressful. The single-unit activity of noradrenergic neurons in the LC of behaving cats was examined under these conditions. The stressful stimuli elicited a significant increase in LC neuronal activity for the entire 15 min stressor duration, whereas the behaviorally activating but nonstressful stimulus elicited no significant change in the activity of these neurons. These results provide evidence that behavioral activation per se is not sufficient to evoke a tonic activation of these neurons. Rather, these data support the hypothesis that the LC is involved in the CNS response to stress and provide additional evidence that the activity of LC noradrenergic neurons increases in association with sympathoadrenal activation.
... Catecholamine cells of the 'main' coeruleal (A6) and 'subcoeruleal' tegmental (A6, A5 and A7) components form a much larger population in M. mulatta and other primates (Hubbard & Di Carlo, 1973;Nobin & Bjorklund, 1973;Felten et al. 1974;Fujita & Tanaka, 1974;Garver & Sladek, 1975;German & Bowden, 1974;Demirjian et al. 1976;Jacobowitz & MacLean, 1978) than noted in the rat (Dahlstrom & Fuxe, 1964;Swanson & Hartman, 1975;Swanson, 1976;Amaral & Sinnamon, 1977). Equivalent neurons in carnivores are also more numerous than in the rat, however in contrast to both the rodent and primates, they form a very diffusely organised 412 SUSAN P. M. SCHOFIELD AND B. J. EVERITT system (Maeda et al. 1973;Chu & Bloom, 1974;Jones & Moore, 1974;Ishikawa et al. 1975;Poitras & Parent, 1978). A similar pattern is seen in the rabbit (Blessing et al. 1978). ...
The distribution of catecholamine neurons in the brains of several rhesus monkeys (Macaca mulatta) was studied by means of the Falck-Hillarp formaldehyde histofluorescence technique. Catecholamine-containing cell bodies in the medulla and pons were found to correspond essentially to the noradrenaline cell groups A1-A7, originally defined in the rat. The pontine catecholamine neurons of the locus coeruleus (A6) and subcoeruleal tegmental areas (A6, A5 and A7) are, however, far more numerous in M. mulatta; observations which agree with reports in other primate species and carnivores. Rostrally projecting fibres, analogous to the ascending 'ventral' and 'dorsal' noradrenaline bundles described in other species, have also been observed in addition to those equivalent to the dorsal periventricular system. The large number of cells present throughout the mesencephalon represent dopamine cell groups A8-A10, while small populations of catecholamine neurons within the periventricular regions of the hypothalamus correspond to groups A11-A14. A prominent terminal innervation of the diencephalon (hypothalamus) is also evident in M. mulatta. Although similar in general terms to that in other species, several important variations are apparent. These and other differences noted above may underlie species specific variations in behaviour.
... The lesions were examined in Nissl-stained sections of the pons (after remaining in formol-saline solution for 10 days, being embedded in paraffin and sectioned at 10/~m thickness). The lesion of each cat was drawn on schematic sections of the dorsolateral pons adopted from Fig. 1 of ref. 28 and quantified (by use of a grid)as per cent destroyed of the area in which noradrenaline locus coeruleus cells are located in A, B, and C of Fig. I. in ref. 28. In addition, the per cent of the lesion (total area) which exceeded the boundaries of the locus coeruleus was calculated. ...
... The lesions were examined in Nissl-stained sections of the pons (after remaining in formol-saline solution for 10 days, being embedded in paraffin and sectioned at 10/~m thickness). The lesion of each cat was drawn on schematic sections of the dorsolateral pons adopted from Fig. 1 of ref. 28 and quantified (by use of a grid)as per cent destroyed of the area in which noradrenaline locus coeruleus cells are located in A, B, and C of Fig. I. in ref. 28. In addition, the per cent of the lesion (total area) which exceeded the boundaries of the locus coeruleus was calculated. ...
The purpose of the present study was to investigate the effects of complete lesions of the noradrenaline locus coeruleus neurons upon wakefulness and paradoxical sleep. Radiofrequency lesions of the nucleus were performed in 8 chronically implanted cats which were continuously recorded with an EEG for 5 days prior to and 21 days following the lesions, when they were sacrified. In 3 of these animals amphetamine (2 mg/kg) was administered on one control day and on the 10th day post-lesion. Following sacrifice, monoamine content was assayed in discrete brain regions, and the lesion was examined in Nissl-stained sections of the pons.(1)The majority (¯x69%) of the locus coeruleus was bilaterally destroyed by the lesions which only minimally exceeded the boundaries of the nucleus within the dorsolateral pontine tegmentum. Noradrenaline was depleted by a mean of 85% in the paleo- and neocortex and by a mean of 60% in the thalamus and midbrain.(2)EEG activation reappeared within 12–48 h following the lesion and represented a normal percentage of recording time on the 3rd and subsequent days post-lesion. The behavioral arousal and long-lasting EEG activation produced by amphetamine was qualitatively and quantitatively the same pre- and post-lesion.(3)Despite alteration of certain components, paradoxical sleep reappeared within 48 h and recovered to normal amounts by the second week post-lesion. Muscle atonia was permanently absent in 7 animals. Ponto-geniculo-occipital (PGO) spiking was acutely redistributed across all states and chronically reduced in frequency (by a mean of 50%) within paradoxical sleep.These results indicate that the noradrenaline locus coeruleus neurons are not necessary for the tonic maintenance of EEG activation that occurs in normal wakefulness and in amphetamine-produced arousal. Furthermore, these neurons are not necessary for the occurrence of paradoxical sleep, although they may be involved in modulation of PGO spiking.
