Deficits in feeding behavior after intraventricular injection of 6-hydroxydopamine in rats.

Intraventricular injections of 6-hydroxydopamine produced 95 percent depletion of telencephalic norepinephrine and 62 percent depletion of striatal dopamine in rats. Treated rats maintained body weight at subnormal levels and failed to increase food intake in response to a short-term decrease in glucose utilization. After treatment with the monoamine oxidase inhibitor pargyline, 6-hydroxydopamine produced no further norepinephrine depletion but increased the dopamnine depletion to 95 percent and produced complete aphagia. These effects are comparable to events that follow bilateral electrolytic lesions of the lateral hypothalanmus.

Brain histamine: rapid apparent turnover altered by restraint and cold stress.

Histamine content of rat brain was lowered quickly by inhibitors of histidine decarboxylase, suggesting that a portion of brain histamine turns over rapidly. Restraint and exposure to cold also reduced brain histamine levels and markedly augmented its formation in the hypothalamus.

Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration.

Neurofibrillary degeneration is an important pathological finding in senile and presenile dementia of the Alzheimer type. Experimentally, aluminum induces neurofibrillary degeneration in neurons of higher mammals. Aluminum concentrations approaching those used experimentally have been found in some regions of the brains of patients with Alzheimer's disease.

Levels of corticotropin releasing factor-like immunoreactivity in mammalian hypothalamic and extrahypothalamic brain tissue as determined with a monoclonal antibody to the ovine material.

A monoclonal antibody to ovine corticotropin releasing factor (CRF) has been produced by fusion of a non-producing plasmacytoma cell line P3U1 with spleen cells of Balb/c mice immunized with the synthetic 41 amino acid peptide coupled covalently with rabbit myosin by a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. A total immunizing dose of 500 micrograms resulted in a highly specific, high-affinity antibody with a Ka of 0.15 x 10(12) M-1, which was used to establish a specific RIA with a sensitivity of 10 pg/tube. Levels of corticotropin releasing factor-like immunoreactivity (CRF-LI) in a pg/mg of hypothalamic tissue ranged from 4-10 in ovine, 2.5-8 in bovine, 47.5-67.5 in mouse and 2.3-20 in human tissue. Moreover, CRF-LI was widely distributed in extrahypothalamic mouse brain at concentrations approximately one half those seen in hypothalamus.

Localization of alpha-melanocyte-stimulating hormone in rat brain and pituitary.

The distribution of alpha-melanocyte-stimulating hormone (alpha-MSH) was studied in the rat brain with an immunoperoxidase technique. alpha-MSH-containing cells were found in the arcuate nucleus of the hypothalamus. Cells staining for alpha-MSH were also localized in the intermediate lobe of the pituitary. alpha-MSH-containing nerve fibers extended throughout regions of the hypothalamus, thalamus, and midbrain. Two weeks after hypophysectomy, alpha-MSH-positive cells anf fibers were still present in the brain. These results indicate that alpha-MSH of non-pituitary origin is synthesized and stored by neural structures in the rat brain. The detection of alpha-MSH by radioimmunoassay in the rat brain and pituitary supports these observations.

Identification and localization of glucagon-like peptide-1 and its receptor in rat brain.

The existence and distribution of glucagon-like peptide-1 (GLP-1) and its receptor in rat brain in relation to that of glucagon were examined. The concentration of GLP-1 immunoreactivity (GLP-1-IR), measured by a specific and sensitive RIA established in this study with anti GLP-1 serum (LMT-01), was found to be highest in the thalamus-hypothalamus, followed by the medulla oblongata. The distribution of glucagon-like immunoreactivity was similar to that of GLP-1-IR. However, appreciable glucagon immunoreactivity was detected only in the thalamus-hypothalamus. Gel filtration analysis showed the presence of GLP-1-IR of various molecular weights in the extract of thalamus-hypothalamus including that eluted at the same position as synthetic GLP-1 (1-37); moreover, HPLC analysis also confirmed the presence of GLP-1-IR, eluted at the exact position as synthetic GLP-1 (1-37). The distribution of receptors for GLP-1 corresponded with that of GLP-1-IR in the rat brain, except in the pituitary gland. The distribution of these receptors was also similar to that of glucagon receptors. The thalamus-hypothalamus, pituitary gland, and medulla oblongata were rich in GLP-1 and glucagon-binding sites. The binding affinities of GLP-1 and glucagon were in the nanomolar range [disocciation constant Kd approximately equal to 4 nM]. The presence of specific, high affinity receptors for GLP-1 was confirmed by demonstrating that GLP-1 stimulated cAMP formation in the thalamus-hypothalamus and the pituitary gland. The concentration of GLP-1 required for half-maximal stimulation of cAMP formation in these regions was about 1 nM. These results suggest that GLP-1 may be synthesized in certain parts of the brain and play a role as a neurosignal transmitter.

Distribution of neurotensin-like immunoreactivity in the diencephalon of the Japanese monkey (Macaca fuscata).

The distribution of neurotensin-like immunoreactive (NT-LI) neurons was examined in the thalamus and hypothalamus of the Japanese monkey (Macaca fuscata) by using the peroxidase-antiperoxidase immunocytochemistry technique. In the thalamus, NT-LI neuronal perikarya were distributed mainly in the midline nuclear group and the dorsomedial nucleus, and partially in the intralaminar nucleus: Immunoreactive fibers were mainly distributed in the midline nucleus, particularly in the nucleus rhomboidalis. Numerous immunoreactive fibers were also detected in the regions that contain the pathways to extrathalamic areas such as the stratum zonale and inferior thalamic peduncle. In the hypothalamus, many immunoreactive neuronal perikarya were distributed in the lateral hypothalamic area and in the arcuate nucleus. Immunoreactive fibers were disseminated throughout the hypothalamus, but they were dense in the preoptic area and sparse in the ventromedial nucleus. An accumulation of dense immunoreactive endings was also observed in the external layer of the median eminence. NT-LI fibers in the external layer of the median eminence were considered to represent nerve endings near portal vessels. Functional roles of neurotensin in the thalamus and hypothalamus are discussed from the anatomical point of view.

Noradrenergic and serotoninergic innervation of cortical, thalamic, and tectal visual structures in Old and New World monkeys.

Antisera directed against human dopamine-beta-hydroxylase and against serotonin were used to characterize the noradrenergic (NA) and serotoninergic (5-HT) innervation of several cortical and subcortical visual areas in squirrel monkey (Saimiri sciureus) and cynomolgus monkey (Macaca fascicularis). Few species differences were observed for either monoamine. Cortical areas 17 and 18, as well as visual areas in the temporal and parietal lobe were found to exhibit regional specialization of both 5-HT and NA innervation. Precisely at the border between areas 17 and 18, the laminar innervation patterns and density characteristic of NA fibers in area 17 (Morrison et al., '82a; Kosofsky et al., '84) shift so that layer IV of area 18 contains more fibers than layer IV of area 17, and the overall density of fibers in area 18 is higher. For 5-HT, the highly laminated patterns characteristic of area 17 (Morrison et al., '82a; Kosofsky et al., '84) also observe this cytoarchitectonic boundary. Fibers in area 18 are more evenly distributed across laminae, and the overall density of fibers decreases. The visual region of the inferotemporal cortex was found to be very lightly innervated by NA fibers and very densely innervated by 5-HT fibers. Area 7 of the parietal lobule was more densely innervated by NA fibers, and less densely innervated by 5-HT fibers, than any other visual cortical region examined. The visual thalamic nuclei exhibited even greater regional differences in the density of NA innervation. The lateral geniculate nucleus was found to be virtually devoid of NA fibers, while the pulvinar-lateral posterior complex was densely innervated. The density of 5-HT fibers was more uniform across thalamic visual nuclei. The lateral geniculate, pulvinar, and lateral posterior nuclei all exhibit a moderate to high density of immunoreactive fibers. In the mesencephalon, the superficial layers of the superior colliculus were found to be densely innervated by NA fibers, whereas 5-HT fibers were most dense in the intermediate layers. These patterns of innervation indicate that, in these primate species, functionally related visual regions share common and distinguishable densities of NA innervation. Specifically, tecto-pulvinar-juxtastriate structures are more densely innervated than geniculo-striate and inferotemporal structures. These relationships suggest that, within the visual system, NA fibers preferentially innervate the regions involved in spatial analysis and visuomotor response rather than those involved in feature extraction and pattern analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of cholecystokinin-immunoreactive cell bodies in the male and female rat: II. Bed nucleus of the stria terminalis and amygdala.

The distribution of cholecystokinin-immunoreactive (CCK-I) cell bodies was studied in the bed nucleus of the stria terminalis (BST) and amygdaloid complex of colchicine-treated male and female rats. Immunoreactive cells were visualized in the BST medial amygdaloid (MeA), central lateral, basolateral, basolateral ventral, medial, intercalated, anterior cortical, and posterior cortical nuclei and the amygdalohippocampal zone. Several significant sex differences were observed. In the male, a dense aggregation of CCK-I cell bodies was visualized in the MeA, especially in the dorsocaudal part and in the encapsulated part of the BST. In comparison, female rats had relatively fewer immunoreactive cells in both of these regions. In the lateral and basolateral amygdaloid nuclei, however, more CCK-I cells were visualized in the female than in the male, but the difference was not statistically significant. These data provide characterization of a sexually differentiated CCK system. In addition, we observed that the number of CCK-I cells in the BST and posterodorsal part of the MeA was substantially reduced after castration. The number of CCK-I cells in female rats, however, was not significantly reduced after ovariectomy in any of the regions studied. These findings imply that the steroid regulation of CCK is sexually differentiated. The sexually dimorphic distribution of CCK-I cells in areas that are targets of steroid hormones and regulate reproductive processes is consistent with the possibility that CCK participates in central integration of sensory and steroidal input that modulates reproductive behavior.

Some aspects of the organization of the thalamic reticular complex.

Anatomical methods which depend upon the anterograde axonal transport of isotopically labeled neuronal proteins or the retrograde axonal transport of the enzyme, horseradish peroxidase, have been used to elucidate the relationships between the reticular complex and the dorsal thalamus and cerebral cortex. Injections of tritiated amino acids in the dorsal thalamus or cerebral cortex in rats, cats and monkeys, show that as the bundles of thalamo-cortical and cortico-thalamic fibers joining a particular dorsal thalamic nucleus to its associated area of the cerebral cortex traverse the reticular complex, they each give rise to a dense zone of terminals occupying a sector of the reticular complex which is relatively constant for that dorsal thalamic nucleus and cortical area. However, because of the wide extent of the dendritic fields of the reticular cells and the degree of overlap between the sectors of the complex subtended by adjacent dorsal thalamic nuclei and adjacent cortical areas, it is likely that the reticular complex samples thalamo-cortical and cortico-thalamic activity in a somewhat unspecific manner. Fibers passing to the reticular complex from the intralaminar nuclei of the thalamus appear to be associated with the projection from the intralaminar nuclei to the striatum. Injections of tritiated amino acids in the reticular complex itself and injections of horseradish peroxidase in various other parts of the brain show that the only efferent pathway from the reticular complex terminates in the nuclei of the dorsal thalamus. The reticular complex does not appear to send fibers to other components of the ventral thalamus nor to the cerebral cortex.

Distribution of neuropeptide Y immunoreactivity in the basal forebrain and upper brainstem of the squirrel monkey (Saimiri sciureus).

The distribution of neuropeptide Y (NPY) immunoreactivity in the brain of the squirrel monkey (Saimiri sciureus) was studied by means of the indirect immunofluorescence, peroxidase-antiperoxidase, and avidin-biotin-complex methods. The antiserum used was raised in rabbits and did not show any significant crossreactivity with related peptides including peptide YY and avian pancreatic polypeptide. In the upper brainstem of the squirrel monkey a dense NPY-immunoreactive terminal field is seen in lateral parabrachial area, locus coeruleus, and interpeduncular nucleus. A small group of NPY-immunoreactive cell bodies is present in the lateral habenula and a moderate number of NPY-immunoreactive fibers occurs in periaqueductal gray and nucleus raphe pallidus. The substantia nigra (SN) appears mostly devoid of NPY immunoreactivity whereas the ventral tegmental area contains a few reactive fibers. In the hypothalamus the medial preoptic area as well as the arcuate and paraventricular nuclei receive a strikingly dense NPY innervation. In addition, numerous NPY-positive cell bodies are found within the dorsomedial half of the supraoptic nucleus but very few are seen in paraventricular nucleus. A large number of NPY-immunoreactive cell bodies is also present in arcuate nucleus. In the basal telencephalon NPY-immunoreactive cells abound mostly in striatum, but some are also found in the amygdala (particularly basal, central, and lateral amygdaloid nuclei), the claustrum, and in the bed nucleus of the stria terminalis. Intensely reactive network of NPY-immunoreactive fibers is also present in all of these structures. In striatum, the numerous, fine and non-varicose NPY-immunoreactive fibers, as well as the NPY-positive cell bodies, are slightly more abundant in caudate nucleus than in putamen. The globus pallidus (GP) is mostly devoid of NPY-immunoreactive fibers and terminals. The fact that the two major recipient structures of striatal outflow (SN and GP) do not receive significant NPY input suggests that the striatal NPY-containing neurons are intrinsically organized.

Age-related changes of catecholamines and their metabolites content in the visual system of the rat.

The changes in the content of the catecholamines in each structure of the geniculate and extrageniculate visual system of the rat during the aging period (6-30 months) have been studied. Dopamine was found at lower levels than noradrenaline in all the structures. The dopamine and noradrenaline showed different developmental profiles. Dopamine and its metabolite levels decreased in the lateral geniculate and visual cortex and increased in superior colliculus and posterior thalamus. Noradrenaline and its metabolites increased in all structures during the aging period. However, 3-methoxy-4-hydroxyphenylglycol/noradrenaline and normetanephrine/noradrenaline ratios decreased in all structures except in superior colliculus. These results suggest age-related changes in the catecholamines in the visual system of the rat.

Localization and quantification of beta-adrenergic receptors in human brain.

Little information is currently available on the localization of noradrenergic systems in the human CNS. We used quantitative autoradiography with [125I] iodopindolol to examine beta-adrenergic receptors in postmortem human brain. The concentration of beta-receptors was highest in all subfields of the hippocampus, followed by cerebellum, and then thalamic nuclei, basal ganglia, midbrain, and cerebral cortex. Low levels were found in white matter and hypothalamus. This distribution differed from the distribution of beta-receptors reported in membrane homogenates of human brain and also from the distribution of beta-receptors in rat brain determined by autoradiography. The similarities and differences between the distribution of beta-receptors in the human and rat brains may have implications regarding the role of norepinephrine in the CNS of these two species.

The effects of N-acetylaspartylglutamate and distribution of N-acetylaspartylglutamate-like immunoreactivity in the rat somatosensory thalamus.

The ventrobasal thalamus and adjacent regions were stained for the presence of N-acetylaspartylglutamate-like immunoreactivity. Immunoreactive axonal terminals were observed in this area and also in certain non-specific thalamic nuclei, the reticular thalamic nucleus and the lateral geniculate nucleus. Stained somata were found in the habenula, centrolateral thalamic nucleus and reticular thalamic nucleus. Iontophoretically applied N-acetylaspartylglutamate had variable, although predominantly inhibitory, actions on ventrobasal thalamus neurons. These results indicate that N-acetylaspartylglutamate is unlikely to be the neurotransmitter of ascending somatosensory afferents, but do not rule out the possibility that it has some other neurotransmitter or neuromodulator role in the ventrobasal thalamus.

Local circuit neurons in the rat ventrobasal thalamus--a GABA immunocytochemical study.

The ventrobasal thalamus of seven rats was processed for immunocytochemistry using antisera to glutamate decarboxylase or gamma-aminobutyrate (GABA). Glutamate decarboxylase-stained sections showed a network of stained fibers and terminals but no stained cell bodies. GABA-stained sections had fewer stained fibers and terminals but did show a few stained cell bodies. Cell bodies were especially apparent when carbazole was used for a chromogen for the peroxidase-antiperoxidase visualization. The GABA-stained cells were found to be distributed throughout the ventrobasal complex, to have smaller soma cross-sectional areas than most other cells (81 +/- 34 microns vs 105 +/- 36 microns for all cells) and to make up 0.4 +/- 0.3% of the neuronal population of the ventrobasal complex. Injections of horseradish peroxidase into the somatosensory cortex (SI) retrogradely filled many neurons in the ventrobasal thalamus, but none of these labeled neurons were double labeled with GABA. These results indicate that the GABA-labeled cells probably represent a small population of local circuit neurons in the rat ventrobasal thalamus.

Effects of chlorpromazine on the metabolism of catecholamines in dog brain.

1. The effect of chlorpromazine (CPZ) on the metabolism of dopamine and 5-hydroxytryptamine in dog brain was investigated by following the concentrations of the acid metabolites of these amines, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid, in the ventricular cerebrospinal fluid (C.S.F.) of dogs over a period of 5 hr after intravenous administration of CPZ (2.5, 5, 10 and 15 mg/kg), using the technique of serial sampling of lateral ventricular C.S.F. "Low" doses (2.5-10 mg/kg) produced a rise in the concentration of homovanillic acid and smaller increases in the concentrations of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid. "High" doses (10-15 mg/kg) had a lesser effect on the concentration of homovanillic acid and had no effect on, or decreased, the concentrations of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid. The concentration of 3,4-dihydroxyphenylacetic acid was maximal in the ventricular C.S.F. 2 hr after CPZ 5 mg/kg and was unaltered from the control level 2 hr after 15 mg/kg.2. The effects on the metabolism of brain amines of CPZ (5 mg/kg), doses which the serial sampling of C.S.F. experiments had indicated as producing maximal and minimal effects on dopamine metabolism in brain tissue, were studied by estimating the concentrations of adrenaline, noradrenaline, dopamine, metanephrine, methoxydopamine, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid in the hypothalamus, midbrain, thalamus, hindbrain, cortex, globus pallidus and caudate nucleus of control dogs and of dogs treated with CPZ intravenously 2 hr before killing. The concentrations of homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid were estimated in samples of ventricular C.S.F. withdrawn from these dogs 2 hr after the injection of CPZ (i.e., immediately before death).3. The following changes in concentrations were observed. Dopamine: CPZ 5 mg/kg produced no change in the concentration in the caudate nucleus, globus pallidus and midbrain and increased the concentration in the thalamus; CPZ 15 mg/kg appeared to cause a reduction in the concentration of this amine in the caudate nucleus and globus pallidus. Homovanillic acid and 3,4-dihydroxyphenylacetic acid: CPZ 5 mg/kg increased the concentrations of both acids in the caudate nucleus and had no effect on the concentrations of the acids in the globus pallidus, hypothalamus and thalamus; CPZ 15 mg/kg produced no change in the concentrations of the acids in any area of the brain. Methoxydopamine: CPZ 5 mg/kg and 15 mg/kg reduced the concentration in the caudate nucleus. Noradrenaline: The concentrations in the hypothalamus, midbrain, thalamus and hindbrain were slightly increased by CPZ 5 mg/kg and 15 mg/kg. Only in the thalamus was a statistically significant increase in noradrenaline observed.4. It was concluded that the actions of chlorpromazine on catecholamine synthesis and metabolism in the brain of the dog are dose dependent. A dose of CPZ 5 mg/kg was postulated to have the following actions: (i) to increase dopamine synthesis; (ii) to activate mitochondrial monoamine oxidase. A dose of CPZ 15 mg/kg was postulated to act as follows: (i) to decrease dopamine synthesis; or (ii) to release dopamine from its storage sites.5. The ratios of the concentrations of homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid in the caudate nucleus to the concentrations of these acids in the ventricular C.S.F. were the same in the control dogs as in the dogs treated with CPZ (5 mg/kg and 15 mg/kg). It was concluded that the levels of the acid metabolites of dopamine in lateral ventricular C.S.F. reflect the levels of these acids in the caudate nucleus.

Effects of intraventricular 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) on rat behaviour and brain catecholamine metabolism.

1. 6-Hydroxydopamine (200 mug injected intraventricularly) caused depletion of noradrenaline from all regions of rat brain within 2 h after injection but depletion of dopamine in the brain was observed only from 2 days after injection. Both catecholamines remained depleted for more than 32 days.2. Rats treated with intraventricular 6-hydroxydopamine were sedated and lethargic, with reduced spontaneous and exploratory activity, for periods of up to 8 days after injection. Conditioned avoidance responding was abolished or reduced for a similar period.3. Intraventricular 6-hydroxydopamine caused a prolonged reduction in the amount of labelled catecholamines in store 4 h following an intraventricular injection of (3)H-dopamine. During the first 6 h after 6-hydroxydopamine injection, there was a marked increase in neutral and acid metabolites from the labelled catecholamines.4. A comparison of the behavioural and biochemical effects of intraventricular 6-hydroxydopamine and reserpine suggests that both drugs affect catecholamine storage mechanisms but by different mechanisms. It was not possible from these experiments to correlate behavioural changes with either catecholamine storage or metabolism.

Concentration of histamine in different parts of the brain and hypophysis of rabbit: effect of treatment with histidine, certain other amino acids and histamine.

1. Estimates have been obtained by biological assay of the histamine concentration in different parts of the rabbit brain and hypophysis.2. Mean values (ng/g) for the brain were: hypothalamus, 660; central grey matter and medial thalamus, 275; tegmental region of mid-brain, the hind-brain and caudate nucleus, 140 to 170; hippocampus and cerebral cortex, 90 to 110; cerebellum (vermis), 60.3. The mean value (ng/g) for the anterior lobe of the hypophysis was 650; for the posterior lobe, 400.4. In conscious rabbits, intravenous infusion of histidine in the dose range 62 to 1,500 mg/kg, raised significantly (P<0.01) the concentration of histamine in all regions of the brain examined, the pattern of distribution remaining unchanged. The largest increases occurred in the mid brain (90 to 320%) and in the hypothalamus (50 to 250%); in these areas the higher doses produced higher concentrations. Elsewhere in the brain the concentration rose in response to the lowest dose of histidine, but was not increased when higher doses were given. Concentrations in the anterior lobe of the hypophysis were unaltered.5. The infusion of histidine, unlike that of amino acid precursors, of the monoamines, produced no obvious disturbance in the animals.6. The rise in brain histamine after dosage with histidine persisted for several hours, depending on the dose; with 500 mg/kg, the rise was virtually unchanged after 16 hours.7. Histamine (5 mg/kg by intravenous infusion) raised the concentration of histamine in the hypophysis but not in the brain.8. After the infusion of DOPA, alpha-methyldopa or 5-hydroxytryptophan, the histamine concentration rose in the mid-brain but not in other parts of the brain.9. These amino acids, when infused singly with histidine, did not interfere with the histidine-induced rise of brain histamine.

Corticotrophin-releasing factor in extra-hypothalamic brain of the mouse: demonstration by immunoassay and immunoneutralization of bioassayable activity.

Corticotrophin-releasing factor (CRF) bioactivity has been described in the extra-hypothalamic brain, but its relationship to hypothalamic CRF has remained questionable. Of the seven regions of the mouse brain examined, highest concentrations of CRF-like immunoreactivity (CRF-LI) and bioassayable CRF activity were present in the median eminence and hypothalamus. However, substantial CRF-LI and bioassayable CRF activity were also seen in brain extracts from the amygdala, thalamus, frontal cortex, pons medulla and cerebellum. Bioactivity was largely neutralized by prior incubation with heat-inactivated antiserum to ovine CRF. These findings, in conjunction with previous immunocytochemical evidence, strongly suggest that a substance closely resembling hypothalamic CRF is present in the extrahypothalamic brain of the mouse.

Distribution of serotonin-immunoreactive neurons in the brain of sockeye salmon fry.

The organization of the serotonergic cell groups in the brainstem of fishes and amphibians has received relatively little attention. It has been generally assumed that they are little differentiated and constitute a median cell column throughout the brainstem, and that laterally migrated serotonergic cell groups are largely lacking. In the present study we present evidence to the contrary. By the use of a sensitive immunocytochemical technique for the visualization of serotonin-immunoreactive (5HTir) neurons, we have been able to make a detailed delineation of the putatively serotonergic neuronal groups throughout the brain. In the epithalamus, 5HTir neurons were located in the left habenular nucleus in its dorsal subdivision. 5HTir neural elements, primarily photoreceptor cells, were present throughout the pineal organ and in some cases also in the parapineal organ. In the periventricular zones of the hypothalamus and posterior tuberculum, 5THir cerebrospinal fluid-contacting neurons were located in the paraventricular organ and in the dorsal, ventral and caudal zones of the periventricular hypothalamus. In the dorsal thalamus/synencephalon, 5THir neurons surround the tractus habenulo-interpeduncularis (fasciculus retroflexus). In the brainstem, several groups of 5HTir neurons could be discerned, that for reasons of topological similarity were named according to Lidov and Molliver a raphe pallidus/obscurus-complex (B1 and B2), raphe magnus (part of B3), median raphe (B8) possibly including raphe pontis (B5), raphe dorsalis (B4, B6 and B7), and B9. 5HTir neurons were observed in the central gray of the IVth ventricle, dorsal to the noradrenergic isthmal neurons and lateral to the brachium conjunctivum, in an area topologically equivalent with the dorsal subdivision of the locus coeruleus in mammals. In addition, small numbers of 5HTir neurons were located in the lobi faciales. Thus, the presence of well-differentiated groups of migrated serotonergic neurons is not an advanced trait of amniote brains, but may be a pattern common to all vertebrates.