Histaminergic neuron system in the brain: Distribution and possible functions

Recent immunocytochemical studies have identified the histaminergic neuron system in the brain. In the rat brain, histaminergic neuronal cell bodies are located in the tuberomammillary nucleus in the posterior hypothalamus, while histaminergic fibers are distributed in almost all regions of the brain. Similar distributions of histaminergic neuronal cell bodies and fibers have been reported in the brains of other mammals and nonmammalian vertebrates. As expected from the widespread distributions of the efferent fibers, the central histaminergic neuron system seems to be involved in multiple functions in the brain. The results of intracerebral injection of histamine and administration of alpha-fluoromethylhistidine (FMH), which depletes brain histamine level, suggest that the central histaminergic system may modulate feeding, drinking and sexual behaviors, sleep-wakefulness and circadian rhythm, neuroendocrine and cardiovascular controls and thermoregulation.     

Organization of the histaminergic system in the brain of the turtle Chinemys reevesii

To accumulate phylogenetic information on the central histaminergic system, we investigated the histaminergic system in the brain of the Reeves turtle, Chinemys reevesii, using the indirect immunofluorescent method with antiserum against histamine. Histaminergic neuronal cell bodies were found exclusively in the posterior part of the ventral hypothalamus. Histaminergic varicose fibers innervated almost all parts of the turtle brain, but tended to be concentrated in several areas. Very dense innervation was observed in the medial part of the telencephalon, ventrolateral part of the hypothalamus, nucleus habenularis lateralis, and ventromedial part of the tegmentum. Medium density of innervation was seen in the olfactory bulb, nucleus medialis amygdalae, and tectum. Only a few fibers were detected in the lateral part of the telencephalon, dorsal part of the hypothalamus, thalamus, rhombencephalon, and spinal cord. The main ascending fibers were observed in the lateral part of the hypothalamus, sending dense fiber bundles to the cortices dorsomedialis and medialis and nucleus habenularis lateralis. Descending fibers appeared to run in the ventral tegmental area, passing through the dorsal and ventral parts of the midline of the brain stem to the spinal cord. These findings indicate that the general morphological features of the histaminergic system in the turtle brain are similar to those in the mammalian and frog brains.     

The histaminergic system in the guinea pig central nervous system: an immunocytochemical mapping study using an antiserum against histamine

Using an antiserum against conjugated histamine we mapped the histaminergic somata and their fiber projection areas in carbodiimide-fixed guinea pig central nervous system. The neurons were large and they were found exclusively in the posterior hypothalamus, as in the rat, but in the guinea pig they were more numerous and distributed more widely in thin layer around the posterior mammillary nucleus, scattered between and within the medial mammillary nuclei, and in a dense cell cluster emerging from the caudal magnocellular nucleus and extending to the medial preoptic area. The density of histamine-immunopositive fibers was very high in the olfactory tubercle, diagonal band of Broca, nucleus accumbens, medial and cortical amygdaloid nuclei, periventricular and lateral basal hypothalamus, paraventricular thalamus, and in a region from the medial central gray to the locus coeruleus and the parabrachial nucleus. Dense fiber networks were found in the piriform and entorhinal cortex, septum, dentate gyrus, and subiculum, in most parts of amygdala, and in many areas of the hypothalamus, thalamus, substantia nigra, raphe nuclei, inferior olivary, solitary tract and medial vestibular nuclei, and neurohypophysis. Medium fiber density was observed in the internal layers of the olfactory bulb, anterior olfactory nuclei, neocortex, zone CA1 of hippocampus, and many midbrain and hindbrain regions. Low density was present in the outer layers of the olfactory bulb, other parts of hippocampus, the globus pallidus, most of the caudatus-putamen, the cerebellar cortex, and the dorsal horn of the spinal cord. The retina and most of the myelinated white matter had single or no histaminergic fibers. It may be concluded from the results that most fibers seem to follow a ventromedial route to the forebrain, reaching the amygdala ventral to the medial forebrain bundle, the hippocampus via subiculum, and the hindbrain structures via the medial central gray. As compared to the rat, the fiber projections in the guinea pig brain were denser, particularly in the hippocampus, thalamus, pons-medulla, and neurohypophysis. The fiber densities in various regions of the guinea pig brain are compared to histamine receptor densities and the possible functions of histamine are discussed.     

Distribution of histaminergic neurons in the brain of the lamprey Lampetra fluviatilis as revealed by histamine-immunohistochemistry

An antiserum against conjugated histamine was used to study the distribution of histaminergic neurons in the CNS of the lamprey Lampetra fluviatilis. Numerous histamine-immunoreactive cell bodies were detected in the dorsal and ventral hypothalamic nuclei and in the adjacent postinfundibular commissural nucleus. Histamine-immunoreactive fibers of high density were present in the ventral hypothalamus, and fibers could also be traced dorsally from the hypothalamus to the corpus striatum and septal nucleus where they appeared to terminate in dense plexuses. Another, smaller group of histamine-immunoreactive perikarya was observed in the border area between mesencephalon and rhombencephalon, near the caudal pole of the mesencephalic reticular nucleus. Sparsely distributed histamine-immunoreactive fibers were present in the ventral mesencephalon. The distribution of histaminergic neurons in cyclostomes, which diverged very early from the main vertebrate line, shows similarities with the corresponding systems in the CNS of amphibians and mammals, which suggests that histaminergic neuronal systems are phylogenetically old and have been conserved during evolution.     

Organization of the histaminergic system in the brain of the teleost, Trachurus trachurus

To accumulate phylogenetic information on the central histaminergic system, we investigated the histaminergic system in the brain of a teleost, the jack mackerel (Trachurus trachurus), using the indirect immunofluorescent method with antiserum against histamine. A small number of histamine-immunoreactive cell bodies were observed in the posterior hypothalamus around the posterior recess. Histamine-immunoreactive fibers innervated the telencephalon, diencephalon, tegmentum, and rostral part of the medulla oblongata. The immunoreactive fibers were very sparse or absent in the olfactory bulb, optic tectum, cerebellum, caudal part of the medulla oblongata, spinal cord, and hypophysis. Ascending fiber bundles were seen in the basal hypothalamus, supplying fiber collaterals to the telencephalon and diencephalon, whereas descending fibers were observed in the midline of the lower brainstem. These findings suggest that the central histaminergic system of the jack mackerel is homologous to those of mammals, reptiles, and amphibians, although poorly developed compared with them. The histamine-immunoreactive neuronal cell bodies found in the border area between the mesencephalon and rhombencephalon of the river lamprey were not detected in the brain of the jack mackerel.     

Histaminergic system in the tree shrew brain

This study mapped the histamine-immunoreactive neuronal system in the brain of the tree shrew (Tupaia belangeri) and compared its structure with that of the rat and guinea pig. The histamine-containing cell bodies lay in the posterior ventral hypothalamus in the tuberomammillary complex, as in the rodents. The morphology of this complex resembled that of the rat. The histaminergic axons projected to nearly all parts of the brain. The main ascending bundle ran ventromedially: the densest innervation was found in the ventral hypothalamus, preoptic area, septum, medial part of nucleus accumbens, and bed nucleus of the stria terminalis. High fiber densities were present in the amygdaloid nuclei and claustrum. Another pathway ran dorsomedially along the periventricular hypothalamus and sent fibers to all parts of the diencephalon. Part of these fibers followed the central gray to the midbrain and spread laterally below the inferior colliculus. Another descending pathway ran through the interfascicular and medial raphe nuclei to meet the pontine central gray. The densest fiber networks were seen in the dorsal tegmental and parabrachial nuclei, and around the locus coeruleus. Also the substantia nigra, interpeduncular and mesencephalic reticular nuclei, colliculi, and vestibular and raphe nuclei received a dense histaminergic innervation. The organization of the fibers in the tree shrew brain resembled more that in the guinea pig than that in the rat. As compared with the guinea pig, more fibers were present, particularly in the globus pallidus, central thalamus, and deep cerebellar nuclei. No fibers were seen in the outer layer of the piriform cortex. In Tupaia, a laminar organization of the fibers was evident in the hippocampus, in contrast to the rodents. Also, a dense periventricular fiber plexus was prominent.     

An altered histaminergic innervation of the substantia nigra in Parkinson's disease

The central histaminergic system is one of the subcortical aminergic projection systems involved in several regulatory functions. The central dopaminergic and histaminergic systems interact extensively, but little is known about the histaminergic system in diseases affecting the dopaminergic neurons. The distribution of histaminergic fibers in the substantia nigra (SN) in postmortem brain samples from patients suffering from Parkinson's disease (PD) and normal controls was examined with a specific immunohistochemical method. Direct connections between dopaminergic neurones and histaminergic fibers were observed. Histamine in human SN was stored in fibers and varicosities. Sites of histamine formation were examined by l-histidine decarboxylase in situ hybridization. In both normal and PD brains HDC mRNA was found only in posterior hypothalamus and not in SN. The presence of histaminergic innervation of the human substantia nigra pars compacta (SNc) and reticulata (SNr), paranigral nucleus, radix of oculomotor nerve, and parabrachial pigmented nucleus was demonstrated. The density of histaminergic fibers in the middle portion of SNc and SNr was increased in brains with PD. In PD the morphology of histaminergic fibers was also altered; they were thinner than in controls and had enlarged varicosities. An increase of histaminergic innervation may reflect a compensatory event due to deficiency of, e.g., dopamine or a putative fiber growth inhibitory factor. Whether the changes seen in histaminergic fibers in PD are primary or secondary remains to be investigated.     

Subicular efferents to histaminergic neurons in the posterior hypothalamic region of the rat studied with PHA-L tracing combined with histidine decarboxylase immunocytochemistry.

The projections from the subiculum to histaminergic cells in the posterior hypothalamic region of the rat were studied by means of anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L) combined with histidine decarboxylase (HDC)-immunohistochemistry. PHA-L was injected at various loci along the dorsoventral and proximodistal axes of the subiculum. This resulted in labeling of the fornix and of terminal plexuses at various locations in the diencephalon and the mammillary body. Following deposition of PHA-L in the proximal part of the dorsal subiculum, labeled fibers in the posterior hypothalamus were confined to the mammillary nuclei, whereas after injections of PHA-L in the distal part of the dorsal subiculum and the entire ventral subiculum, labeled fibers were also present in clusters of histaminergic cells located around the mammillary nuclei. The density of the PHA-L labeled fibers within these clusters increased from low to moderate in association with a shift of the injection sites from dorsal to ventral and from proximal to distal parts of the subiculum, i.e., the highest fiber labeling was seen after injections of PHA-L in the distal part of the ventral subiculum. In the latter experiments, PHA-L labeled fibers reached HDC-immunoreactive neurons in the tuberal magnocellular nucleus, the deepest layer of the caudal magnocellular nucleus, the two bridges of histaminergic cells in the posterior hypothalamus, and the histaminergic neurons scattered in the supramammillary region. A few labeled fibers invaded the postmammillary caudal magnocellular nucleus. The presence of varicosities on the PHA-L labeled fibers in close proximity to the cell bodies and dendrites of the histaminergic neurons suggest the existence of synaptic contacts.     

Histamine immunoreactive neurons in the brain stem of the rabbit

Distribution of histamine-like immunoreactive (HA-LI) neurons in the rabbit brain stem was demonstrated by histamine antiserum. A number of HA-LI cell bodies were localized in the tuberomammillary nucleus of the posterior hypothalamus. A dense to moderate amount of HA-LI fibers was found distributed in the raphe nuclei, the inferior olive, the nucleus of the solitary tract, vestibular nuclei, and the paragigantocellular reticular nucleus in the medulla oblongata, and the parabrachial nuclei, the Klliker-Fuse nucleus, the pontine nuclei, and the locus coeruleus in the pons. HA-LI axons synapsed on dendrites of neurons in the nucleus of the solitary tract. This evidence suggests that histaminergic neurons control neuronal activity through synaptic transmission in the lower brain stem.     

Vasopressin innervation of sexually dimorphic structures of the gerbil forebrain under various hormonal conditions.

The distribution of vasopressin-immunoreactive fibers in the forebrain of male and female gerbils was studied, focusing on the lateral septum and the sexually dimorphic area (SDA) found at the border between the medial preoptic area and the anterior hypothalamus. To study hormonal influences on the densities of these fibers, some animals of each sex were gonadectomized or gonadectomized and given testosterone. Others were given sham operations. High densities of vasopressin-immunoreactive fibers were found in the lateral septum. In the SDA, the densities of these fibers varied considerably. Many were found in the medial half of the medial SDA, but few in the lateral SDA. Vasopressin-immunoreactive fibers were also sparse in the lateral half of the medial SDA, except for a dense cluster in the SDA pars compacta of males. Similar but smaller clusters were seen in the same location in females although the SDA pars compacta could not be detected in Nissl-stained sections from the female brains. Fiber densities in two areas, the lateral septum and the lateral SDA, were sensitive to gonadal steroids. In both cases, castration reduced fiber density and testosterone enhanced it. In addition, fiber densities in two areas, the lateral septum and the medial SDA, were sexually dimorphic. In each case, fiber density was greater in males. There was no hormonal effect, however, on the fiber densities in the medial SDA. The fact that the fiber plexuses in the lateral septum and the medial SDA respond differently to gonadal steroids suggests that they arise from different cells and possibly from different areas of the brain. The vasopressin-immunoreactive fibers in the lateral septum probably come from steroid-sensitive vasopressin neurons in the bed nucleus of the stria terminalis. Those in the medial SDA may originate in the dorsal aspect of the suprachiasmatic nucleus where vasopressin-immunoreactive cell bodies were seen.     

Innervation of histaminergic neurons in the posterior hypothalamic region by medial preoptic neurons. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunocytochemistry of histidine decarboxylase in the rat

By means of anterograde neuroanatomical tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) combined with immunohistochemistry of histidine decarboxylase (HDC), we studied in the rat whether the histaminergic neurons in the posterior hypothalamic region are innervated by fibers arising from neurons in the medial preoptic region (MPO). We injected the tracer at various locations in the MPO. Following survival, frozen brain sections were dual-stained according to a protocol using PHA-L and HDC immunocytochemistry. From all parts of the MPO, PHA-L-labeled fibers course to ipsi- and contralateral clusters of histaminergic neurons located in the posterior hypothalamus. Varicosities on the PHA-L-labeled fibers can be observed in close association with HDC-immunoreactive cell bodies and dendrites in all the histaminergic cell clusters in the posterior hypothalamus. These associations suggest synaptic connectivity.     

Anatomical distribution of LHRH-immunoreactive neurons in the human infant hypothalamus and extrahypothalamic regions

The morphological features and distribution of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cell bodies and fibers of the hypothalamic and the neighboring mesencephalic regions were studied in the normal newborn infant by immunohistochemistry. Within the hypothalamus, numerous LHRH-immunoreactive like (IL) cell bodies were found mainly in the ventral portion of the infundibular nucleus close to the median eminence and at a lower extent in the medial preoptic area. In addition, sparse immunoreactive cell bodies were displayed in the paraventricular and medial mammillary nuclei. The mesencephalon also exhibited rare immunoreactive cell bodies in the periaqueductal gray. LHRH-IL fibers, predominantly varicose, formed a continuum from the septo-preoptico level to the mesencephalon. In the hypothalamus, the median eminence exhibited the highest LHRH innervation. LHRH-IL fibers are also observed in the lamina terminalis, the medial preoptic area, the suprachiasmatic, the supraoptic, the peri- and the paraventricular nuclei. In the last two nuclei, some fibers projected to the dorsomedial and ventromedial nuclei whereas others were in close relation with the ependyma. The mesencephalon displayed low LHRH-IL fibers, present essentially in the raphe and interpeduncular nuclei and around the ependyma. When compared with data obtained in other mammals, the present findings agree well with the general distribution and morphological features of LHRH-IL neuronal structures reported elsewhere.     

Histamine-immunoreactive nerve fibers in the rat pineal gland: evidence for a histaminergic central innervation

An immunohistochemical method that utilizes carbodiimide as a fixative and antisera directed against histamine was applied to investigate the location of histamine in the rat pineal complex. Numerous histamine-immunoreactive cell bodies were observed in different subdivisions of the tuberomammillary nucleus of the posterior hypothalamus, and a few cell bodies were present in the posterior and dorsal part of the periventricular hypothalamic nucleus. Histamine-immunoreactive fibers were observed to leave the posterior hypothalamus in various directions of which one dorsally projecting tract was followed in the periventricular area of the caudal diencephalon to the epithalamus. Several histamine-immunoreactive nerve fibers of this tract continued through the posterior commissure directly into the deep pineal gland. A few immunoreactive fibers were also observed in the habenular commissure. In midsagittal sections, histamine-immunoreactive nerve fibers were observed to enter the pineal stalk from the deep pineal gland. Most of histamine-immunoreactive fibers in the stalk continued towards the superficial pineal gland, but their number decreased in more distal locations of the stalk, indicating that some fibers terminate in the stalk as well. A few fibers were found to terminate in the most rostral part of the superficial pineal gland. The immunoreactive nerve fibers in the epithalamus and pineal complex were endowed with prominent varicosities. Taken together, these results indicate that histaminergic nerve fibers, originating from the posterior hypothalamus, project to the pineal complex of the rat. Histamine must therefore be considered a putative neurotransmitter contained in the central innervation of the pineal gland, but its function in pineal physiology has so far not been elucidated.     

Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation.

Hibernation in mammals such as the rodent hibernator Citellus lateralis is a physiological state in which CNS activity is endogenously maintained at a very low, but functionally responsive, level. The neurotransmitter histamine is involved in the regulation of diurnal rhythms and body temperature in nonhibernators and, therefore, could likely play an important role in maintaining the hibernating state. In this study, we show that histamine neuronal systems undergo major changes during hibernation that are consistent with such a role. Immunohistochemical mapping of histaminergic fibers in the brains of hibernating and nonhibernating golden-mantled ground squirrels (C. lateralis) showed a clear increase in fiber density during the hibernating state. The tissue levels of histamine and its first metabolite tele-methylhistamine were also elevated throughout the brain of hibernating animals, suggesting an increase in histamine turnover during hibernation, which occurs without an increase in histidine decarboxylase mRNA expression. This hibernation-related apparent augmentation of histaminergic neurotransmission was particularly evident in the hypothalamus and hippocampus, areas of importance to the control of the hibernating state, in which tele-methylhistamine levels were increased more than threefold. These changes in the histamine neuronal system differ from those reported for the metabolic pattern in other monoaminergic systems during hibernation, which generally indicate a decrease in turnover. Our results suggest that the influence of histamine neuronal systems may be important in controlling CNS activity during hibernation.     

Distribution of phenylethanolamine-N-methyltransferase-immunoreactive perikarya and fibers in the brain of the lizard Gekko gecko

The distribution of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive (PNMTi) cell bodies and fibers in the brain of the lizard Gekko gecko was studied by antibodies raised in rabbits against purified bovine adrenal PNMT. The PNMTi cell bodies were observed in the ventrolateral rhombencephalic tegmentum at the level of the obex. No immunoreactive perikarya were found in the nucleus of the solitary tract, the medial longitudinal fascicle or the hypothalamus. An extensive network of PNMTi fibers is present throughout the brain, extending rostrally as far as the olfactory peduncle. In the telecenphalon, moderate to dense plexuses of PNMTi fibers were observed in the medial part of the nucleus accumbens, the medial septal nucleus, the nucleus of the diagonal band, the caudoventral septal region and the central amygdaloid nucleus. In the diencephalon, the periventricular and lateral zones of the preoptic and hypothalamic areas, the medial forebrain bundle and the dorsomedial thalamic nucleus contain many PNMTi fibers. Brainstem structures innervated by PNMTi fibers are the ventral tegmental area, the substantia nigra, the periaqueductal gray, the locus coeruleus, the parabrachial region, the nucleus of the solitary tract, the dorsal motor nucleus of the vagus and the ventrolateral region of the caudal brainstem. Although the brain of Gekko appears to lack PNMTi cells in areas comparable to the C2 and C3 cell groups in rats, the distribution of PNMTi fibers is nevertheless strikingly similar in both groups.     

Distribution of parvalbumin-immunoreactive cells and fibers in the monkey temporal lobe: The amygdaloid complex

The calcium-binding protein parvalbumin was immunohistochemically localized in the monkey amygdaloid complex. Parvalbumin-immunoreactive neuronal cell bodies, fibers, and terminals were observed in several amygdaloid nuclei and cortical areas. Three types of aspiny neurons, ranging from small spherical cells (Type 1) to large multipolar cells (Type 2) and fusiform cells (Type 3) were observed in most amygdaloid regions, though the proportions of the cell types were different in each region. The density of parvalbumin-immunoreactive fibers and terminals tended to parallel the density of labeled cell bodies. The highest densities of parvalbumin profiles were observed in the nucleus of the lateral olfactory tract, the periamygdaloid cortex (PAC2), the magnocellular division of the basal nucleus, the ventrolateral portion of the lateral nucleus, and the accessory basal nucleus. The regions containing the lowest densities of parvalbumin-positive profiles were the medial nucleus, anterior cortical nucleus, central nucleus, and the paralaminar nucleus. In regions with fiber and terminal labeling, pericellular networks of fibers, reminiscent of basket cell terminations, were commonly observed to surround unstained neuronal cell bodies and proximal dendrites. In the magnocellular division of the basal nucleus, and to a lesser extent in the lateral nucleus, parvalbuminlabeled “cartridges” of axo-axonic terminals were observed on the initial segments of unlabeled cells. Parvalbumin-positive varicosities were also commonly observed in close apposition to the soma and dendrites of parvalbumin-immunoreactive cells. Given the close correspondence between the distribution of parvalbumin-positive neurons and a subset of GABAergic neurons in many brain regions, these data provide a first indication of the organization of the inhibitory circuitry of the primate amygdaloid complex. © 1993 Wiley-Liss, Inc.     

Histamine turnover in regions of rat brain

Rapid and complete inhibition of monoamine oxidase by pargyline produced linear increases in the content of the histamine metabolite, tele-methylhistamine (t-MH), in 9 regions of rat brain 2 and 4 h after drug administration. The treatment had little or no effect on the histamine content of these regions. As histamine methylation is the major metabolic pathway of histamine in brain, the rate of increase in brain t-MH content after complete inhibition of its metabolism provides an estimate of histamine turnover. Histamine turnover rates varied over 46-fold among regions, from cerebellum (0.029 nmol/g . h) to hypothalamus (1.33 nmol/g . h), similar to those reported for norepinephrine and serotonin. Turnover rates were highly correlated with control t-MH levels (r = 0.97) and control histamine levels (r = 0.84). Rate constants were highest in the caudate nucleus and frontal cortex, equivalent to a half-life of about 11 min in these regions. While hypothalamic histamine had the highest turnover rate, the rate constant for histamine in this region was among the lowest in brain, perhaps consistent with the presence of histaminergic cell bodies. Histamine turnover rates may be indicative of the activity of histamine-synthesizing neurons, and their determination will facilitate understanding of histamine in brain.     

Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal,motivation, and stress

A double-label immunohistochemical study was carried out to investigate overlap between dopamine-beta-hydroxylase (DbetaH) -immunopositive projections and the projections of hypothalamic neurons containing the arousal- and feeding-related peptide, orexin/hypocretin (HCRT), in rat brain. Numerous intermingled HCRT-immunopositive and DbetaH-immunopositive fibers were seen in a ventrally situated corridor extending from the hypothalamus to deep layers of the infralimbic cortex. Both fiber types avoided the nucleus accumbens core, caudate putamen, and the globus pallidus. In the diencephalon, overlap was observed in several hypothalamic areas, including the perifornical, dorsomedial, and paraventricular nuclei, as well as in the paraventricular thalamic nucleus. Intermingled HCRT-containing and DbetaH-containing fibers extended from the hypothalamus into areas within the medial and central amygdala, terminating at the medial border of the lateral subdivision of the central nucleus of the amygdala. Dense overlap between the two fiber types was also observed in the periaqueductal gray, particularly in the vicinity of the dorsal raphe, as well as (to a lesser extent) in the ventral tegmental area, the retrorubral field, and the pedunculopontine tegmental nucleus. Hypocretin-containing cell bodies, located in the perifornical and lateral hypothalamus, were embedded within a dense plexus of DbetaH-immunopositive fibers and boutons, with numerous cases of apparent contacts of DbetaH-containing boutons onto HCRT-immunopositive soma and dendrites. HCRT-containing fibers were observed amid the noradrenergic cells of the locus coeruleus, and in the vicinity of the A1, A2, and A5 cell groups. Hence, the projections of these two arousal-related systems, originating in distinctly different parts of the brain, jointly target several forebrain regions and brainstem monoaminergic nuclei involved in regulating core motivational processes.     

Distribution of galanin-like immunoreactivity in the brain of Rana esculenta and Xenopus laevis.

The immunocytochemical distribution of galanin-containing perikarya and nerve terminals in the brain of Rana esculenta and Xenopus laevis was determined with antisera directed toward either porcine or rat galanin. The pattern of galanin-like immunoreactivity appeared to be identical with antisera directed toward either target antigen. The distribution of galanin-like immunoreactivity was similar in Rana esculenta and Xenopus laevis except for the absence of a distinct laminar distribution of immunoreactivity in the optic tectum of Xenopus laevis. Galanin-containing perikarya were located in all major subdivisions of the brain except the metencephalon. In the telencephalon, immunoreactive perikarya were detected in the pars medialis of the amygdala and the preoptic area. In the diencephalon, immunoreactive perikarya were detected in the caudal half of the suprachiasmatic nucleus, the nucleus of the periventricular organ, the ventral hypothalamus, and the median eminence. In the mesencephalon, immunoreactive perikarya were detected near the midline of the rostroventral tegmentum, in the torus semicircularis and, occasionally, in lamina A and layer 6 of the optic tectum. In the myelencephalon, labelled perikarya were detected only in the caudal half of the nucleus of the solitary tract. Immunoreactive nerve fibers of varying density were observed in all subdivisions of the brain with the densest accumulations of fibers occurring in the pars lateralis of the amygdala and the preoptic area. Dense accumulations of nerve fibers were also found in the lateral septum, the medial forebrain bundle, the periventricular region of the diencephalon, the ventral hypothalamus, the median eminence, the mesencephalic central gray, the laminar nucleus of the torus semicircularis, several laminae of the optic tectum, the interpeduncular nucleus, the isthmic nucleus, the central gray of the rhombencephalon, and the dorsolateral caudal medulla. The extensive system of galanin-containing perikarya and nerve fibers in the brain of representatives of two families of anurans showed many similarities to the distribution of galanin-containing perikarya and nerve fibers previously described for the mammalian brain.