Localization of serotonin in the hypothalamus and the mesencephalon of the guinea-pig

Summary The distribution of serotonin in the hypothalamus and the mesencephalon of guinea-pigs pretreated with both pargyline and L-tryptophan was investigated immunohistochemically using monoclonal antibodies to 5-HT. 5-HT-positive fibers and varicosities appeared distributed throughout the hypothalamus. Some areas showed a greater density of immunoreactivity: the suprachiasmatic nucleus, the region of the supraoptic crest, the area of the medial forebrain bundle, the ventral part of the nucleus ventromedialis, the median eminence and the ventral part of the mammillary bodies. 5-HT nerve fibers were also scattered in the posterior lobe of the pituitary. An extensive supraependymal plexus of immunoreactive axons was observed in most ventricular regions. No 5-HT positive cell bodies were present in the hypothalamus of the guinea-pig under our experimental conditions, whereas an intense serotonin immunoreactivity was detected in perikarya of the brain stem. 5-HT cell bodies were found predominantly in the raphe region including the nucleus raphe dorsalis and raphe medianus, nucleus interpeduncularis, reticular formation and dorsal area of the medial lemniscus.     

Calcitonin gene-related peptide: detailed immunohistochemical distribution in the central nervous system

With the use of an antiserum generated in rabbits against synthetic human calcitonin gene-related peptide (CGRP) the distribution of CGRP-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system. A detailed stereotaxic atlas of CGRP-like neurons was prepared. CGRP-like immunoreactivity was widely distributed in the rat central nervous system. CGRP positive cell bodies were observed in the preoptic area and hypothalamus (medial preoptic, periventricular, anterior hypothalamic nuclei, perifornical area, medial forebrain bundle), premamillary nucleus, amygdala medialis, hippocampus and dentate gyrus, central gray and the ventromedial nucleus of the thalamus. In the midbrain a large cluster of cells was contained in the peripeduncular area ventral to the medial geniculate body. In the hindbrain cholinergic motor nuclei (III, IV, V, VI, VII XII) contained CGRP-immunoreactivity. Cell bodies were also observed in the ventral tegmental nucleus, the parabrachial nuclei, superior olive and nucleus ambiguus. The ventral horn cells of the spinal cord, the trigeminal and dorsal root ganglia also contained CGRP-immunoreactivity. Dense accumulations of fibers were observed in the amydala centralis, caudal portion of the caudate putamen, sensory trigeminal area, substantia gelatinosa, dorsal horn of the spinal cord (laminae I and II). Other areas containing CGRP-immunoreactive fibers are the septal area, nucleus of the stria terminalis, preoptic and hypothalamic nuclei (e.g., medial preoptic, periventricular, dorsomedial, median eminence), medial forebrain bundle, central gray, medial geniculate body, peripeduncular area, interpeduncular nucleus, cochlear nucleus, parabrachial nuclei, superior olive, nucleus tractus solitarii, and in the confines of clusters of cell bodies. Some fibers were also noted in the anterior and posterior pituitary and the sensory ganglia. As with other newly described brain neuropeptides it can only be conjectured that CGRP has a neuroregulatory action on a variety of functions throughout the brain and spinal cord.     

The distribution pattern of alpha-MSH-like immunoreactivity in the cat central nervous system

The distribution pattern of alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-Li) was studied in cats using avidin-biotin modification of immunocytochemical method. Cell bodies containing alpha-MSH-Li were observed in the medial basal hypothalamus, especially in the infundibular nucleus, the lateral hypothalamus and near zona incerta. Fibers with alpha-MSH-Li extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus ceruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. Axons with alpha-MSH-Li were also seen diffusely in various cortical areas, but more extensively in the limbic cortical regions. The distribution pattern of the cell bodies and fibers containing alpha-MSH-Li bears several similarities to that seen in rats, but differs in that the alpha-MSH-Li was not observed in cell bodies in locations other than the medial basal and lateral hypothalamus.     

Morphology of neuroglia in the hypothalamus of the opossum (Didelphis virginiana), armadillo (Dasypus novemcinctus mexicanus) and cat (Felis domestica)

The hypothalamus of the opossum (Didelphis virginiana), the armadillo (Dasypus novemcinctus mexicanus), and the cat (Felis domestica) was studied using Del Rio Hortega's silver carbonate technique, as modified by Scharenberg ('60). This technique demonstrates astrocytes, oligodendroglia, and neuronal perikarya, but does not impregnate microglia. The morphology of macroglia was observed in ten comparable nuclei in each of the three species. The subpial and subependymal areas were also examined. Astrocytes display more cell body angularity and have more processes in most hypothalamic regions of the cat when compared to similar regions of the opossum and armadillo. In the anterior hypothalamic nucleus, the ventromedial and the dorsomedial hypothalamic nuclei, and the medial mammillary nucleus of all three species, astrocytes send processes to neurons, but neuronal and astrocytic perikarya are usually not directly contiguous. However, oligodendrocytes in a perisomatic position on neurons are a consistent feature in these nuclei. A closer relationship appears to exist between astrocytes and neurons in the neurosecretory nuclei. In the supraoptic nucleus and paraventricular nucleus of all three species a basket-like structure, designated a ?pericellular envelope”? was observed surrounding neuronal perikarya. This structure is composed of astrocytic and oligodendroglial cell bodies and processes, and is most highly developed in the cat. A dense astrocytic plexus was observed in the suprachiasmatic nucleus of the cat, and in the comparable nuclei of the armadillo and opossum. The most prominent macroglial cell type of the lateral hypothalamic and lateral mammillary nuclei of all three species is the interfascicular oligodendrocyte. The posterior hypothalamic nucleus of each species has many perisomatic oligodendrocytes, and in the armadillo and cat astrocytes are closely related to the larger neurons. A subpial plexus, consisting of a palisade of small glial cells with many processes, is present in the hypothalamus of the three species. Ependymal cells have long projecting processes throughout the length of the third ventricle in the armadillo hypothalamus, but such processes are only apparent in the region of the infundibular nucleus and median eminence in the opossum and cat.     

Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study

The presence of central cannabinoid receptor (CB1), involving the N-terminal 14 amino acid peptide, was demonstrated in the rat brain by immunohistochemistry. Intensely stained neurons were observed in the principal neurons of the hippocampus, striatum, substantia nigra, cerebellar cortex, including the Purkinje cells. Moderate CB1-IR cell bodies and fibers were present in the olfactory bulb, cingulate, entorhinal and piriform cortical areas, amygdala and nucleus accumbens. The perivascular glial fibers have shown moderate to high density CB1-IR in olfactory and limbic structures. Low density was detected in the thalamus and hypothalamus and area postrema. The CB1 receptor was widely distributed in the forebrain and sparsely in the hindbrain. These new data support the view that the endogenous cannabinoids play an important role in different neuronal functions as neuromodulators or neurotransmitters.     

Retinohypothalamic projections and immunocytochemical analysis of the suprachiasmatic region of the desert iguana Dipsosaurus dorsalis

Two separate and distinct retinal projections to the hypothalamus in the iguanid lizard Dipsosaurus dorsalis were described using horseradish peroxidase and cobalt-filling techniques. Both of the projections were unilateral and completely crossed; one terminated in the supraoptic nucleus and the other in the suprachiasmatic nucleus. Immunocytochemical analysis showed that the supraoptic nucleus contained cell bodies and fibers that cross-react with antibodies raised against arginine vasopressin, while the suprachiasmatic nucleus contained arginine vasopressin-like immunoreactive fibers emanating from cells in the nearby paraventricular nucleus. The suprachasmatic nucleus contained a dense plexus of fibers that cross-reacted with neuropeptide-Y antibody. Antiserum against vasoactive intestinal polypeptide showed no reactivity in any part of the forebrain, while antiserum against serotonin showed sparse and uniform reactivity throughout the forebrain, including the suprachiasmatic nucleus. These results, together with other data, indicate that the suprachiasmatic nucleus of D. dorsalis is homologous to the suprachiasmatic nuclei of rodents, structures known to contain circadian pacemakers. We suggest that the suprachiasmatic nucleus may play a similar role in the circadian system of D. dorsalis.     

Distribution of neuropeptide Y immunoreactivity in the forebrain of the rat

The distribution of neuropeptide Y (NPY) like immunoreactivity was investigated in the forebrain of the rat with immunohistochemical methods. Specificity of the antisera was established by the absence of all immunoreactive staining in tissue incubated in antisera which had been preabsorbed with the pure NPY antigen. NPY containing cells were distributed widely in the forebrain. These included neocortex, basal forebrain, septum, bed nucleus of the stria terminalis, neostratium, hypothalamic arcuate nucleus, and intergeniculate leaflet. This study also demonstrated an extensive network of NPY fibers in various areas of the forebrain such as the prepotic area, the hypothalamus and the paraventricular nucleus of the thalamus. The distribution of avian pancreatic polypeptide and NPY was compared, and the possible importance of NPY is briefly discussed.     

Histamine-immunoreactive neurons in the hypothalamus of cats

The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine-immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus.     

Immunohistochemical mapping of galanin-like neurons in the rat central nervous system

Using an antiserum generated in rabbits against synthetic galanin (GA) and the indirect immunofluorescence method, the distribution of GA-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system (CNS) and a detailed stereotaxic atlas of GA-like neurons was prepared. GA-like immunoreactivity was widely distributed in the rat CNS. Appreciable numbers of GA-positive cell bodies were observed in the rostral cingulate and medial prefrontal cortex, the nucleus interstitialis striae terminalis, the caudate, medial preoptic, preoptic periventricular, and preoptic suprachiasmatic nuclei, the medial forebrain bundle, the supraoptic, the hypothalamic periventricular, the paraventricular, the arcuate, dorsomedial, perifornical, thalamic periventricular, anterior dorsal and lateral thalamic nuclei, medial and central amygdaloid nuclei, dorsal and ventral premamillary nuclei, at the base of the hypothalamus, in the central gray matter, the hippocampus, the dorsal and caudoventral raphe nuclei, the interpeduncular nucleus, the locus coeruleus, ventral parabrachial, solitarii and commissuralis nuclei, in the A1, C1 and A4 catechaolamine areas, the posterior area postrema and the trigeminal and dorsal root ganglia. Fibers were generally seen where cell bodies were observed. Very dense fiber bundles were noted in the septohypothalamic tract, the preoptic area, in the hypothalamus, the habenula and the thalamic periventricular nucleus, in the ventral hippocampus, parts of the reticular formation, in the locus coeruleus, the dorsal parabrachial area, the nucleus and tract of the spinal trigeminal area and the substantia gelatinosa, the superficial layers of the spinal cord and the posterior lobe of the pituitary. The localization of the GA-like immunoreactivity in the locus coeruleus suggests a partial coexistence with catecholaminergic neurons as well as a possible involvement of the GA-like peptide in a neuroregulatory role.     

Distribution of GABA-immunoreactive neurons in the forebrain of the goldfish,Carassius auratus

Summary The distribution of gamma-aminobutyric acid (GABA) immunoreactivity was studied in the forebrain (tel-and diencephalon) of the goldfish by means of immunocytochemistry on Vibratome sections using antibodies against GABA. Positive perikarya were detected in the olfactory bulbs and in all divisions of the telencephalon, the highest density being found along the midline. In the diencephalon, GABA-containing cell bodies were found in the hypothalamus, in particular in the preoptic and tuberal regions. The inferior lobes, the nucleus recessus lateralis, and more laterodorsal regions, such as the nucleus glomerulosus and surrounding structures, also exhibited numerous GABA-positive perikarya. Cell bodies were also noted in the thalamus, in particular in the dorsomedial, dorsolateral and ventromedial nuclei. The relative density of immunoreactive fibers was evaluated for each brain nucleus and classified into five categories. This ubiquitous distribution indicates that, as in higher vertebrates, GABA most probably represents one of the major neurotransmitters in the brain of teleosts.     

Oxytocin immunoreactivity in the hypothalamus of female hamsters

In Syrian hamsters (Mesocricetus auratus), oxytocin (OXT) activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays an important role in the expression of sexual receptivity. Immunocytochemical analysis with OXT-specific antibodies was used to identify the distribution of OXT-containing cell bodies and fibers in female hamster brain and to determine the possible sources of OXT important for sexual receptivity. Oxytocin-immunoreactive cell bodies and fibers were found in several regions of the preoptic area, including the medial preoptic area, the medial preoptic nucleus, and the bed nucleus of the stria terminalis. Large numbers of cell bodies and fibers were localized within the paraventricular and supraoptic nuclei, and in anterior hypothalamus. OXT-immunoreactive fibers were observed in the VMH and the ventral tegmental area. The anatomical data from the present study support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.     

Neuropeptide Y localization in telencephalic and diencephalic structures of the ground squirrel brain

The distribution of neuropeptide Y-immunoreactive (NPY-IR) perikarya, fibers, and terminals was investigated in the brain of two species of hibernatory ground squirrels, Spermophilus tridecemlineatus and S. richardsonii, by means of immunohistochemistry. In the telencephalic and diencephalic structures studied, distinct patterns of NPY-IR were observed which were essentially identical in male and female animals of both species. No differences in amount or distribution of NPY-IR structures were observed between animals which had been in induced hibernation for several months before sacrifice in March/April and those sacrificed one week after their capture in May. In some brain structures (e.g., the hypothalamic arcuate nucleus), IR cell bodies were observed only after pretreatment with colchicine. NPY-IR perikarya and fibers were found in the cerebral cortex, caudate nucleus-putamen, and dorsal part of the lateral septal nucleus. Dense fiber plexuses were seen in the lateral and medial parts of the bed nucleus of the stria terminalis. The numbers of IR perikarya observed in the medial part of the nucleus increased following intraventricular colchicine injections. The accumbens nucleus exhibited few IR cells and many fibers. Claustrum and endopiriform nuclei showed a considerable number of stained cells and fibers that increased in number and staining intensity in colchicine-treated ground squirrels. The induseum griseum showed a small band of IR cell bodies and varicose fibers. Bipolar of multipolar IR cells and varicose fibers were found in the basal nucleus of the amygdala. Dense fiber plexuses as well as IR terminals were seen in the median, medial, and lateral preoptic areas of the hypothalamus. Terminals and relatively few fibers were located in the periventricular, paraventricular, and supraoptic nuclei. The anterior, lateral, dorsomedial, and ventromedial hypothalamic nuclei contained relatively large numbers of terminals and fibers. In the suprachiasmatic nuclei, dense terminals were distributed mainly in the ventromedial subdivision. In the median eminence, immunoreactive terminals were concentrated in the external layer, with fibers predominant in the internal layer. NPY-IR perikarya were observed only in the arcuate nucleus of the hypothalamus and only following colchicine treatment. In the epithalamus (superficial part of the pineal gland and habenular nuclei), varicose fibers appeared mainly in perivascular locations (pineal) or as a dense plexus (habenular nuclei). These results from ground squirrels are discussed in comparison to those obtained in other species and with regard to considerations of the physiological role of NPY.     

A fluorescence microscopic study of the distribution of monoamines in the hypothalamus of the cat

Three distinct groups of monoamine (MA)-containing nerve cell bodies have been visualized in the hypothalamus and preoptic area of the cat by means of the Falck-Hillarp fluorescence histochemical technique. First, numerous small-sized catecholamine (CA) type neurons were disclosed within the ventral half of the periventricular area in the supraoptic and middle hypothalamic regions. The round to oval neurons of this medio-ventral group were more especially abundant around the base of the third ventricle, within the arcuate and supraopticus diffusus nuclei. Numerous medium-sized CA perikarya identified as the dorsal group, were also mapped out in the dorsal and posterior hypothalamic areas. Finally, a small population of both CA and serotonin (5-hydroxytryptamine, 5-HT)-containing neurons was disclosed within the lateral area of the middle and mammillary hypothalamic regions. These multipolar or elongated neurons which compose the lateral group were lying either along the ventrolateral surface of the hypothalamus or around the ventrolateral aspect of the fornix. In addition to these three MA cell groups, a few cells displaying a fluorescence of the CA type were also visualized in the so-called “dorsal chiasmatic nucleus” after α-methyl-dopa treatment. High density of CA axon terminals were found, on the other hand, in the external layer of the median eminence, in the dorsomedial, paraventricular, supraoptic and suprachiasmatic nuclei, and also within nucleus interstitialis of stria terminalis. In the present study, however, it was not possible to identify with certainty any concentration of 5-HT axon terminals in the cat hypothalamus. Therefore, except for the lateral cell group which could be peculiar to the cat, the topographical distribution of MA nerve cell bodies and axon terminals in the hypothalamus of the cat appears similar to the morphological organization of the MA neuronal elements in the hypothalamus of the rat.     

FMRFamide-like immunoreactivity in the brain of the Pacific hagfish,Eptatretus stouti (Myxinoidea)

Summary The distribution of FMRFamide-like immunoreactivity was investigated in the brain of a myxinoid, the Pacific hagfish,Eptatretus stouti, by means of immunocytochemistry. In the forebrain, labelled cell bodies occurred in the infundibular nucleus of the hypothalamus and some closely adjacent nuclei. Labelled fibers formed a diffuse network in the forebrain, but there was no evidence for the presence of intracerebral ganglionic cells of the terminal nerve or a central projection of the terminal nerve. In the hindbrain, a group of labelled cells was found in the trigeminal sensory nucleus. A distinet terminal arborization occurred in the ventrally adjacent nucleus A of Kusunoki and around the nuclei of the branchial motor column. These findings suggest that FMRFamide may play a role in the central control of branchiomotor activity.     

Distribution of atrial natriuretic factor-like immunoreactivity in the brain of the frog Rana ridibunda

The localization of atrial natriuretic factor (ANF)-like immunoreactivity in the central nervous system of the frog Rana ridibunda was examined by the indirect immunofluorescence technique, using an antiserum against synthetic ANF (Arg101-Tyr126). Immunoreactive cell bodies were principally found in the dorsal and medial pallium, the medial septal nucleus, the ventrolateral and anteroventral areas of the thalamus, the lateral forebrain bundle, the posterolateral thalamic nuclei, the preoptic nucleus, the dorsal infundibular nucleus, and the anteroventral tegmentum nucleus of the mesencephalon. Numerous cell bodies and a very dense fiber bundle were visualized in the interpeduncular nucleus. All the areas mentioned above contained a high density of immunoreactive fibers. In addition, the amygdala, the infundibular nucleus, the median eminence, and most of the areas of the mesencephalon contained a moderate number of ANF-positive nerve processes. In the frog pituitary, fibers and nerve terminals were found in the peripheral zone of the neural lobe. The intermediate and anterior lobes of the frog pituitary were totally devoid of ANF immunoreactivity. These results indicate that ANF-like material is widely distributed in the frog brain and that ANF may be involved in various brain functions including neuroendocrine regulations.     

Neurotensin-like immunoreactivity in the diencephalon of the adult male cat

Using an indirect immunoperoxidase technique, the location of neurotensin-like fibers and cell bodies was studied in the diencephalon of the cat. The findings showed that the hypothalamus is richer in neurotensin-like-immunoreactive structures than the thalamus, and that neurotensin-like-immunoreactive structures are more widely distributed in the hypothalamus than in the thalamus. A high density of immunoreactive fibers was observed in the hypothalamic regions, area hypothalamica dorsalis, hypothalamus posterior, nucleus (n.) filiformis and n. arcuatus, whereas a moderate density was found in the n. parafascicularis, n. paraventricularis anterior, hypothalamus lateralis, median eminence and n. paraventricularis hypothalami. Other diencephalic regions such as n. lateralis posterior, n. lateralis dorsalis, n. medialis dorsalis, n. habenularis lateralis, n. centrum medianum, n. rhomboidens, n. reuniens, hypothalamus anterior, n. supra chiasmaticus, hypothalamus ventromedialis, n. supraopticus and hypothalamus dorsomedialis had the lowest density of immunoreactive fibers. In addition, the densest clusters of neurotensin-like perikarya were found in the n. arcuatus, n. centralis medialis and hypothalamus posterior, whereas the n. medialis dorsalis, n. paraventricularis anterior, n. reuniens, hypothalamus lateralis and hypothalamus ventromedialis had the lowest density. In the n. lateralis dorsalis, n. supraopticus, area hypothalamica dorsalis and n. supra chiasmaticus the density of immunoreactive perikarya was moderate.     

Localization of ACTH in the human hypothalamus

Summary Using an antiserum to porcine ACTH and the unlabeled antibody peroxidase-antiperoxidase technique, we have found that ACTH is present in neuronal cell bodies located exclusively in the arcuate nucleus of the human hypothalamus. ACTH-containing fibers are distributed extensively throughout the hypothalamus with the greatest density in the periventricular nucleus. No concentration of ACTH fibers could be observed in the neurovascular zone of the pituitary stalk.     

Light-microscopic immunocytochemical localization of growth hormone-releasing factor in the human hypothalamus

Summary The distribution of growth hormone-releasing factor (GRF)-like immunoreactivity in the human hypothalamus was studied by light-microscopic immunocytochemistry. With antibodies that we developed against synthetic human pancreatic GRF (hpGRF), we localized GRF immunoreactivity in neuronal cell bodies that were observed only in the infundibular (arcuate) nucleus. Immunostained nerve fibers were found in large numbers in the neurovascular zone of the median eminence, in the proximal portion of the pituitary stalk and in periventricular areas. These localizations are in agreement with those of studies recently performed in other species and strongly suggest that GRF can be released into the capillaries of the pituitary portal plexus to reach the anterior pituitary gland. The projections of GRF neurons in extra-infundibular regions suggest that GRF can also act as a neuromodulator or neurotransmitter in the hypothalamus.     

Distribution of gastrin and CCK-like peptides in rat brain

Summary The distribution of gastrin and CCK-like peptides in the rat brain was studied by immunocytochemistry using an antiserum reacting equally well with both groups of peptides. Immunoreactive nerve cell bodies were detected in all cortical areas, in the hippocampus where they were particularly numerous, in the mesencephalic central gray and in the medulla oblongata. After colchicine treatment immunoreactive material appeared also in cell bodies of the magnocellular hypothalamic system. Immunoreactive nerve fibers were widely distributed in the brain. Particularly dense accumulations were seen in the hippocampus near the ventral surface of the brain, in the caudate nucleus, in the interpeduncular nucleus, the parabrachial nucleus, the dorsal part of the medulla oblongata and in the dorsal horn of the spinal cord. In the hypothalamus immunoreactive nerve fibers were observed in all nuclei, being most frequent in the ventromedial, dorsal and lateral hypothalamic nuclei. A rich supply of nerve fibers was seen in the outer zone of the median eminence and in the neurohypophysis. From previous immunochemical analysis it appears that the peptide demonstrated in most parts of the brain is identical with CCK-8. In the neurosecretory cell bodies of the hypothalamus, the median eminence and the neurohypophysis, however, the immunoreactive material is probably identical with gastrin.     

Neuropeptide-Y and ACTH-immunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat. An immunocytochemical analysis at the light and electron microscopic levels

Corticotropin releasing factor (CRF), synthesized in neurons of the hypothalamic paraventricular nucleus (PVN), is one of the main regulators of the pituitary-adrenal cortex endocrine axis. In order to elucidate the possible involvement of the central neuropeptide-Y (NPY)- and adrenocorticotroph hormone (ACTH)-immunoreactive (IR) systems in the innervation of hypophysiotrophic CRF-synthesizing neurons, immunocytochemical double labelling studies were conducted in the hypothalamus of the rat to localize CRF-synthesizing neurons, as well as neuronal fibers exhibiting NPY and ACTH-immunoreactivity, respectively. The parvocellular subnuclei of the PVN received an intense NPY- and ACTH-IR innervation. At the light microscopic level, these peptidergic axons were associated with the dendrites and perikarya of CRF-IR neurons. Ultrastructural analysis revealed that NPY- and ACTH-IR axons established synaptic specializations with parvocellular neurons expressing CRF-immunoreactivity. These findings indicate that both neuropeptide-Y and adrenocorticotroph hormone containing neuronal systems of the brain are capable of influencing adrenal function via synaptic interactions with hypophysiotrophic CRF-synthesizing neurons. The data also support the concept that NPY and ACTH might be utilized as neuromodulators within the PVN.