Neuropeptide Y-immunoreactive neurons in the striatum of cat and monkey: Morphological characteristics, intrinsic organization and co-localization with somatostatin

A detailed study of the distribution of neuropeptide Y (NPY) in the striatum of squirrel monkey (Saimiri sciureus) and cat was undertaken by means of indirect immunofluorescence and peroxidase-antiperoxidase (PAP) methods. In monkey, the NPY-immunoreactivity is homogeneously distributed along the entire extent of the caudate nucleus (CD) and putamen (PUT), while in cat marked heterogeneities are noted. In the CD of cat, the NPY-immunoreactive fibers and cell bodies are concentrated in numerous patches of various sizes, which can be readily distinguished from zones of poor NPY-immunostaining. In the CD and PUT of squirrel monkey the NPY-positive neurons are either triangular, fusiform or globular, with long and smooth dendrites branching infrequently. The numerical density of NPY-immunoreactive cell bodies is greater in the CD than in the PUT, and it increases markedly along the rostrocaudal extent of the striatum. In the rostral CD and PUT the densities are 23 cells/mm2 and 14 cells/mm2, respectively, whereas the values for caudal CD and PUT are 35 cells/mm2 and 20 cells/mm2, respectively. Quantitative measurements reveal that these NPY-immunoreactive cells belong to a single subset of striatal neurons having a maximum diameter of 19.2 +/- 0.1 micron and a cross-sectional area of 145.5 +/- 0.6 micron2 (mean +/- S.E.M.; n = 1238 CD cells and 1169 PUT cells). Furthermore, experiments combining the use of lectin-conjugated HRP as retrograde tracer with PAP immunohistochemical method demonstrate that striatal NPY-immunoreactive neurons in squirrel monkey and cat do not project outside the striatum. Finally, co-localization studies in monkey reveal that the vast majority of striatal NPY-positive neurons also contains somatostatin. These results show that the NPY-immunoreactive neurons in mammalian striatum form a subpopulation of medium-sized interneurons containing somatostatin.     

Mapping of neuropeptide Y-like immunoreactivity in the feline hypothalamus and hypophysis

The distribution of neuropeptide Y (NPY) in the cat hypothalamus and hypophysis was studied with the indirect immunofluorescence technique of Coons and co-workers (Coons, Leduc, and Connolly: J. Exp. Med. 102:49-60, 1955), which provided a detailed map of NPY-like immunoreactive neurons. The immunolabelling was detected in cell bodies, fibers, and terminallike structures widely distributed throughout the whole hypothalamus. A large population of medium-sized NPY-like immunoreactive cell bodies was localized in the area of arcuate nucleus. The number of immunoreactive cell bodies visualized was dramatically increased after intracerebroventricular injections of colchicine. Numerous immunolabelled cell bodies were also visible in the median eminence and scattered in the lateral hypothalamic area. Dense plexuses of NPY-immunoreactive fibers were observed in the arcuate nucleus, internal layer of median eminence, periventricular zone, and paraventricular nucleus. Other regions of hypothalamus displaying numerous NPY-like immunoreactive fibers included dorsal and ventrolateral hypothalamic areas. In contrast, certain hypothalamic areas were almost devoid of NPY-like immunoreactive fibers-namely, the mammillary bodies and suprachiasmatic nucleus. Finally, in neurohypophysis, bright immunofluorescent fibers were observed along the pituitary stalk and penetrating the neural lobe. These results suggest the widespread distribution of the NPY-containing neuronal systems in the cat hypothalamus and hypophysis.     

Directional cues for arcuate NPY projections are present in the adult brain

Arcuate nucleus neuropeptide Y (NPY) neurons project within the hypothalamus and to several extrahypothalamic brain areas. Plasticity in the formation of arcuate NPY projections established postnatally may underlie the phenotypic characteristics of food intake and body weight. In this work we determined if directional cues for axonal outgrowth of NPY arcuate neurons exist in the adult brain. For this purpose, an embryonic (E15) arcuate nucleus of WT mice was grafted into the third ventricle of 2-week- and 2-month-old NPY knockout (KO) mice. One month after the transplantation, the distribution of NPY-positive terminals in the brains of NPY-KO mice was studied using immunohistochemistry. NPY-positive terminals were found inside of the grafted tissue as well as in the host hypothalamus, including the arcuate nucleus, the paraventricular and periventricular nuclei, the lateral hypothalamic and preoptic areas, and in extrahypothalamic areas such as the amygdala and the thalamic paraventricular nucleus. This pattern of distribution of NPY fibers was found in both groups of grafted mice. The brain areas reinnervated by NPY-positive terminals in the NPY-KO mice closely corresponded to the normal targets for the arcuate NPY neurons as revealed by the distribution of agouti gene-related protein immunoreactivity. Our data show that directional cues for NPY arcuate nucleus projections are present in the adult brain, suggesting their involvement in the formation of normal arcuate NPY connections and a possibility for their functional reconstruction.     

Decreased NPY innervation of the hypothalamic nuclei in rats with cancer anorexia

Whether the decrease in food intake that occurs at the onset of anorexia in tumor bearing (TB) rats is related to a change in the hypothalamic neuropeptide Y (NPY) system was tested by comparing NPY expression in sham operated Fischer Control and anorectic TB rats. Coronal cryocut sections of their fixed brain were processed by the peroxidase-antiperoxidase method with NPY polyclonal antibodies. NPY-immunoreactive fibers were widely distributed throughout the forebrain, but were most prominent in the hypothalamic paraventricular, suprachiasmatic, arcuate and periventricular nuclei. NPY-immunoreactive neurons were visualized in Control and anorectic TB rats in the preoptic region, the arcuate nucleus, and occasionally in the lateral hypothalamus. Semiquantitative image analysis showed a significant decrease in the NPY immunostaining in some hypothalamic nuclei of the anorectic TB rats, most prominently in the supraoptic nucleus, the parvocellular portion of the paraventricular nucleus, and, to a lesser extent, the suprachiasmatic and arcuate nuclei. No changes in NPY innervation were seen in the ventromedial nucleus and the lateral hypothalamus. The data support the hypothesis of an altered hypothalamic NPY system at the onset of anorexia in TB rats and also reveal the hypothalamic nuclei through which NPY influences food intake.     

Effects of monosodiuml-glutamate administration on neuropeptide Y-containing neurons in the rat hypothalamus

Immunocytochemical localization of neuropeptide Y (NPY) was performed in the hypothalamus of rats of which the arcuate nucleus had been destroyed with monosodiuml-glutamate in the neonatal period. The treatment produced a disappearance of most of the NPY cell bodies normally found in the arcuate nucleus. The concentration of fibers was decreased in the paraventricular nucleus, but not in the other hypothalamic nuclei. The treatment also induced the appearance of a large number of immunoreactive cell bodies in the paraventricular nucleus. These results strongly suggest that arcuate NPY neurons are projecting to the paraventricular nucleus and that the arcuate nucleus probably exerts some inhibitory tonic influence on NPY paraventricular neurons.     

Effects of monosodium L-glutamate administration on neuropeptide Y-containing neurons in the rat hypothalamus

Immunocytochemical localization of neuropeptide Y (NPY) was performed in the hypothalamus of rats of which the arcuate nucleus had been destroyed with monosodium L-glutamate in the neonatal period. The treatment produced a disappearance of most of the NPY cell bodies normally found in the arcuate nucleus. The concentration of fibers was decreased in the paraventricular nucleus, but not in the other hypothalamic nuclei. The treatment also induced the appearance of a large number of immunoreactive cell bodies in the paraventricular nucleus. These results strongly suggest that arcuate NPY neurons are projecting to the paraventricular nucleus and that the arcuate nucleus probably exerts some inhibitory tonic influence on NPY paraventricular neurons.     

Differential response of arcuate proopiomelanocortin- and neuropeptide Y-containing neurons to the lesion produced by gold thioglucose administration

The effect of gold thioglucose (GTG) administration on neurons containing feeding-related peptides in the hypothalamic arcuate nucleus was examined in mice. Intraperitoneal GTG injection increased the body weight and produced a hypothalamic lesion that extended from the ventral part of the ventromedial nucleus to the dorsal part of the arcuate nucleus. Neurons containing proopiomelanocortin (POMC) and neuropeptide Y (NPY) present in the dorsal part of the arcuate nucleus were destroyed by GTG. In addition, the peptide-containing fibers that extended from the remaining arcuate neurons were degenerated at the lesion site. The number of POMC-containing fibers in the paraventricular nucleus, dorsomedial nucleus, and lateral hypothalamus was found to have decreased significantly when examined at 2 days and 2 weeks after the GTG treatment. In contrast, the number of NPY-containing fibers in the lateral hypothalamus remained unchanged after the GTG treatment, probably because of the presence of an unaffected NPY-containing fiber pathway passing through the tuberal region and projecting onto the lateral hypothalamus. The number of NPY-immunoreactive fibers in the paraventricular and dorsomedial nuclei showed a moderate but significant decrease at 2 days after the GTG treatment, but it recovered to the normal levels 2 weeks later. The NPY-containing fibers were found to have regenerated across the lesion site 2 weeks later, and this might contribute to the recovery of the NPY-immunoreactive fibers in these regions. The present results first demonstrate that POMC- and NPY-containing neurons in the arcuate nucleus respond differently to the lesion produced by the GTG treatment.     

Distribution of enkephalin-immunoreactive neurons in the forebrain and upper brainstem of the squirrel monkey

The distribution of enkephalin-immunoreactive neuronal profiles in the forebrain and upper brainstem of the squirrel monkey (Saimiri sciureus) was studied by means of the indirect immunofluorescence method. Numerous enkephalin-immunoreactive cell bodies and fibers were disclosed in various regions including cerebral cortex, hippocampus, caudate nucleus, putamen, nucleus accumbens, septal area, olfactory tubercle, substantia innominata, amygdala, various hypothalamic and thalamic nuclei, periaqueductal gray, midbrain reticular formation and interpeduncular nucleus. Some of the highest concentrations of enkephalin-positive fibers in the squirrel monkey brain were found in the external segment of the globus pallidus, the outer layer of the median eminence, and in the pars reticulata of the substantia nigra. Overall, the pattern of distribution of the enkephalin-immunoreactive cell bodies and fibers in the forebrain and upper brainstem of the squirrel monkey is similar to that found in the rat, except that the density of positive neuronal profiles in the entire forebrain appears much higher in monkey than in rat. Furthermore, the very dense network of enkephalin-immunoreactive fibers disclosed in the substantia nigra pars reticulata of monkey appears to be lacking in rat.     

Localization and characterization of neuropeptide Y in the brain of Microcebus murinus (Primate, Lemurian)

The distribution of neuropeptide Y (NPY) in the brain of the lemur Microcebus murinus was determined by immunocytochemistry with the aid of a highly specific antiserum against synthetic porcine NPY. When compared with previous immunohistochemical data obtained in primates and other mammalian species, the localization of NPY-immunoreactive (IR) structures in the Microcebus murinus brain revealed particular features. (1) Numerous NPY-IR perikarya and a dense network of IR nerve terminals were found in the supraoptic and suprachiasmatic nuclei, respectively. The occurrence of NPY-IR perikarya in the supraoptic nucleus, also reported in the squirrel monkey, seems to be specific to primates. In the squirrel monkey, the suprachiasmatic nucleus exhibits only a moderate innervation, whereas in humans it appears totally devoid of NPY-IR fibers. (2) IR perikarya and axon processes were observed in many upper brainstem areas, in particular in the interpeduncular, raphe pontine, dorsal tegmental, parabrachial, and dorsal raphe nuclei, in the locus coeruleus, the nucleus of the solitary tract, and the reticular formation; in this latter area, the occurrence of two categories of NPY-IR neurons was demonstrated on the basis of their morphology and localization, suggesting that they may play distinct roles. (3) NPY-IR nerve processes could be traced over a long distance. (4) For the first time, numerous NPY-IR terminals were observed close to the lumen of the various cerebral ventricles. The immunoreactive NPY-like peptide was characterized by combining high performance liquid chromatography (HPLC) analysis and radioimmunoassay quantification. The dilution curves obtained with synthetic porcine NPY and serial dilutions of occipital cortex, paraventricular and supraoptic hypothalamus, posterior hypothalamus, medulla oblongata, or preoptic area extracts were parallel. The highest amounts of NPY were measured in the hypothalamus and telencephalon. HPLC analysis resolved a single peak of NPY-like immunoreactivity that exhibited the same retention time as synthetic porcine NPY. The distribution of NPY in the lemurian brain is discussed with respect to phylogeny and putative functions.     

Localization of neuropeptide Y mRNA and peptide in the chicken hypothalamus and their alterations after food deprivation, dehydration, and castration.

Localization of neuropeptide Y (NPY) mRNA in the hypothalamus of chickens was studied by in situ hybridization with digoxigenin-labeled chicken NPY cRNA probe. The largest number of perikarya-expressing NPY mRNA was found within the mediobasal hypothalamus, including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence. Many NPY perikarya were noted to surround the nucleus rotundus and to be present in the supraoptic nucleus. Moreover, some perikarya were detected in the nucleus of basal optic root, bed nucleus pallial commissure, and nucleus striae terminalis close to the lateral forebrain bundle. NPY-immunoreactive nerve fibers were densely distributed in these regions containing the NPY mRNA-expressing perikarya. Following food deprivation for four days, perikarya-expressing NPY mRNA and peptide were markedly increased in the mediobasal hypothalamus and particularly so in the infundibular nucleus. No changes, however, were detected in other regions containing NPY-positive perikarya. Water deprivation induced less increase in NPY-positive perikarya in the mediobasal hypothalamus compared to food deprivation. After gonadectomy, the number of NPY-positive perikarya in the mediobasal hypothalamus was unaltered. Northern blot analysis with (32)P-labeled chicken NPY cDNA probe demonstrated that a 2.7-fold increase of NPY mRNA was induced by starvation and a 1.5-fold increase was induced by dehydration, whereas the NPY mRNA band remained unchanged after gonadectomy. Thus, it seems that NPY neurons located in the mediobasal hypothalamus are involved in feeding behavior but not reproductive activity.     

Dopaminergic innervation of the basal ganglia in the squirrel monkey as revealed by tyrosine hydroxylase immunohistochemistry

The organization of the dopaminergic mesostriatal fibers and their patterns of innervation of the basal ganglia in the squirrel monkey (Saimiri sciureus) were studied immunohistochemically with an antiserum raised against tyrosine hydroxylase (TH). Numerous fibers arose from midbrain TH-positive cell bodies of the substantia nigra pars compacta (group A9), the retrorubral area (group A8), and the lateral portion of the ventral tegmental area (group A10). These fibers accumulated dorsomedially to the rostral pole of the substantia nigra where they formed a massive bundle that coursed through the prerubral field and ascended along the laterodorsal aspect of the medial fore-brain bundle in the lateral hypothalamus. Some ventrally located fibers ran throughout the rostrocaudal extent of the lateral preopticohypothalamic area and could be followed up to the olfactory tubercle, whereas other fibers turned laterodorsally to invade the head of the caudate nucleus. At more dorsal levels in the lateral hypothalamus, many fiber fascicles detached themselves from the main bundle and swept laterally to reach the globus pallidus, the putamen, and the amygdala. Several TH-positive fibers coursed along the dorsal surface of the subthalamic nucleus, and some invaded the dorsomedial third of this structure. The remaining portion of the subthalamic nucleus contained relatively few TH-positive elements. In contrast, the globus pallidus received a dense dopaminergic innervation deriving mostly from two fascicles that coursed backward along the two major output pathways of the pallidum: the lenticular fasciculus caudodorsally and the ansa lenticularis rostroventrally. At the pallidal level, the labeled fibres merged within the medullary laminae and arborized profusely in the internal pallidal segment and less abundantly in the external pallidal segment. However, the caudoventral portion of the external pallidum displayed a dense field of TH-positive axonal varicosities. Other fibers ran through the dorsal two-thirds of the external pallidum en route to the putamen. The striatum contained a multitude of thin axonal varicosities among which a few long and varicosed fibers were scattered. These immunoreactive neuronal profiles were rather uniformly distributed along the rostrocaudal extent of the striatum but appeared slightly more numerous in the ventral striatum than in the dorsal striatum. The pattern of distribution of the TH-positive axonal varicosities in the dorsal striatum was markedly heterogeneous: it consisted of typical zones of poor TH immunoreactivity lying within a matrix of dense terminal labeling.(ABSTRACT TRUNCATED AT 400 WORDS)     

Differential dopaminergic innervation of the two pallidal segments in the squirrel monkey (Saimiri sciureus)

Immunohistochemical studies with an antiserum raised against tyrosine hydroxylase have allowed us to demonstrate a dense dopaminergic innervation of the globus pallidus in the squirrel monkey. This innervation derived mostly from two fascicles that detached themselves from the major ascending dopaminergic bundle arising from midbrain dopamine cell bodies and running in the lateral hypothalamus. Dopaminergic fibers reached the globus pallidus by coursing along its two major output pathways: the lenticular fasciculus dorsally and the ansa lenticularis ventrally. At pallidal levels, dopaminergic fibers abounded in medullary laminae and arborized profusely within the internal pallidal segment, whereas the external pallidum displayed only few short fibers that prevailed in its dorsal portion. These findings provide the first evidence that the primate globus pallidus receives a massive and diffentially distributed dopaminergic input.     

Distribution of immunoreactive substance P neurons in the hypothalamus and pituitary of the rhesus monkey

The distribution of immunoreactive substance P (IR-SP) neurons was examined in the hypothalamus and pituitary gland of the rhesus monkey by using the peroxidase-antiperoxidase immunocytochemical technique. Immunoreactive SP cell bodies were observed in the arcuate nucleus, in the region lateral to the arcuate nucleus, and in the median eminence (ME). Immunoreactive SP cells were also seen in the periventricular area of the dorsal tuberal region. A rich network of SP fibers was concentrated in the arcuate region, and the fiber stain was particularly dense in the external zone of the median eminence and in the external layer of the infundibular stalk. Also, substance P fibers were seen in the internal layer of the pituitary stalk and in the neural lobe of the pituitary gland. Outside the hypothalamus a dense network of IR-SP fibers was observed in the globus pallidus.     

Distribution of neuropeptide Y-like immunoreactivity in the hypothalamus of the adult golden hamster

The distribution of neuropeptide Y (NPY)-like immunoreactivity within the hypothalamus of the adult golden hamster was investigated with conventional immunohistochemical techniques. Neuropeptide Y immunoreactive cell bodies were found in greatest numbers in the arcuate nucleus while a few stained perikarya were seen in the internal and subependymal zones of the median eminence. Isolated perikarya were observed in the anterior commissure and supracommissural portion of the interstitial nucleus of the stria terminalis. Immunoreactive axons were located throughout the hypothalamus with the highest concentrations in the subependymal and internal zones of the median eminence, the interstitial nucleus of the stria terminalis, the medial preoptic area, and in the following nuclei: periventricular, suprachiasmatic, paraventricular, perifornical, median preoptic, and arcuate. Moderate to dense plexuses of immunoreactive fibers were observed in the anterior, lateral, and posterior hypothalamic areas and in the infundibular stalk. The supraoptic nucleus and lateral preoptic area displayed a small number of labeled axons whereas the ventromedial nucleus contained only a few fibers. NPY immunoreactive fibers were present in the optic tract and in the dorsomedial aspect of the optic chiasm. Labeled fibers penetrated the ependymal lining of the third ventricle throughout the ventral aspect of the periventricular zone. Additional fibers were observed in the pia lining the ventral aspect of the hypothalamus. This systematic analysis of hypothalamic NPY immunoreactivity in the adult golden hamster suggests that a portion of the labeled fibers display a distribution that is similar to previously described noradrenergic fibers in the hypothalamus.     

Neuropeptide tyrosine in the brain of the African lungfish,Protopterus annectens: Immunohistochemical localization and biochemical characterization

Lungfishes, which share similarities with both fishes and amphibians, represent an interesting group in which to investigate the evolutionary transition from fishes to tetrapods. In the present study, we have investigated the localization and biochemical characteristics of neuropeptide Y (NPY)-immunoreactive material in the central nervous system of the African lungfish, Protopterus annectens. NPY-immunoreactive cell bodies were found in various regions of the brain, most notably in the telencephalon (septal area, ventral striatum, and nucleus accumbens), in the diencephalon (preoptic nucleus, periventricular region of the hypothalamus, and ventral thalamus), and in the tegmentum of the mesencephalon. A strong immunoreaction was also detected in cell bodies of the nervus terminalis. Immunoreactive nerve fibers were particularly abundant in the ventral striatum, the nucleus accumbens, the diagonal band of Broca, the hypothalamus, and the mesencephalic tegmentum. Positive fibers were also seen in the median eminence and in the neural lobe of the pituitary. The NPY-immunoreactive material localized in the brain and pituitary was characterized by combining high-performance liquid chromatography (HPLC) analysis and radioimmunological quantitation. The displacement curves obtained with synthetic porcine and frog NPY and serial dilutions of brain and pituitary extracts were parallel. Reversed-phase HPLC analysis of telencephalon, diencephalon, and pituitary extracts resolved a major NPY-immunoreactive peak that coeluted with frog NPY. The similarity between the distribution of NPY-containing neurons and the biochemical characteristics of the immunoreactive peptide in the brain of lungfish and frog strongly favors a close phylogenetic relationship between dipnoans and amphibians. © 1995 Wiley-Liss, Inc.     

Distribution of Acetylcholinesterase-Containing Neurons in the Basal Forebrain and Upper Brainstem of the Squirrel Monkey (Saimiri sciureus)

The topographical distribution of neurons containing acetylcholinesterase (AChE, EC 3.1.1.7) in the basal forebrain and upper brainstem of the squirrel monkey (Saimiri sciureus) was studied by means of Butcher's pharmacohistochemical technique which involves staining for AChE at various times after the systemic administration of the AChE inhibitor di-isopropylphosphorofluoridate (DFP). Only those neurons whose AChE staining was as intense as that of known cholinergic neurons present in the same material (e.g., neurons of cranial nerve nuclei) were examined and mapped. Three major collections of such strongly-stained AChE neurons were disclosed in squirrel monkey brain: one located in the striatum, the other lying along the ventralmost aspects of the basal forebrain, and a third one present within the midbrain-pontine tegmentum. The striatal AChE neurons vary in shape from fusiform with 2 thick processes to polygonal with 4-5 thinner processes. They are uniformly scattered throughout the caudate nucleus and putamen and represent only a small proportion of the total striatal cell population (4-6 cells/mm2). They most likely correspond to the aspiny type II cells described in Golgi material of monkey striatum. Similar neurons occur also in ventral striatal areas comprising nucleus accumbens septi and the deep polymorph layer of the olfactory tubercle. The second major AChE neuronal population is composed of the magnocellular neurons that form a somewhat continuous chain of neuronal aggregates extending rostrocaudally from the septal region to the caudal pole of the lentiform nucleus. It includes the neurons of the medial septal nucleus, the nucleus of the diagonal band of Broca and the nucleus basalis of Meynert, all displaying strikingly similar morphological and histochemical characteristics. The AChE neuronal population of nucleus basalis encroaches markedly upon the lateral hypothalamus laterally and the globus pallidus dorsally. The third important AChE cell collection occurs within the pedunculopontine nucleus area in upper brainstem. In that constellation, the AChE neurons are clustered in 2 continuous cell groups: one located dorsolaterally, the other lying ventromedially to the brachium conjunctivum. The thick processes of these neurons form impressive AChE neuronal networks that surround and pervade the brachium conjunctivum over long distances. This cell group, which is one of the most highly AChE reactive structures of the entire brain in the squirrel monkey, may provide a major cholinergic input to various basal ganglia structures, particularly the substantia nigra.     

Distinct adenosine deaminase-containing inputs to the substantia nigra from the striatum and tuberomammillary nucleus

Immunohistochemical, neuroanatomical and lesion methods were used to investigate the projections of adenosine deaminase immunoreactive (ADA-IR) neurons in the striatum (caudate/putamen) and hypothalamus to the substantia nigra (SN). Striatal ADA-IR neurons were distributed within two zones; anteriorly in the medial and ventromedial extreme of the head and body of the striatum, and posteriorly in the tail of the striatum. The posterior hypothalamus contained ADA-positive neurons which were confined to the tuberomammillary nucleus (TM). The SN was devoid of ADA-positive neurons, but contained two distinct types of ADA-IR fiber terminations. One type was confined to bands located at the ventrolateral and dorsomedial borders of the pars reticulata and consisted of fine puncta. The other type was distributed throughout the SN and consisted of long, beaded fibers. Injections of the retrograde tracer Fluoro-gold (FG) into the SN gave rise to FG-labelling of significant numbers of ADA-IR neurons in both the striatum and TM. Medial SN injections preferentially labelled ADA-IR neurons in the anterior striatum and lateral SN injections labelled posterior ADA-IR striatal neurons. Kainic acid lesions of the anterior medial striatum selectively abolished the punctate ADA-IR band in the medial SN and left the long, ADA-IR nigral fibers in an apparently hypertrophied state. Despite depletion of ADA-IR neurons in the striatum by kainic acid, ADA activity increased significantly at striatal lesion sites. The results suggest that the SN receives two topographically segregated fine terminal fields from striatal ADA-IR neurons, and a substantial innervation from ADA-IR neurons in the TM as well. These findings add to the heterogeneous chemical composition of nigral afferents and are discussed in the context of adenosine neuromodulatory mechanisms in the striatonigral system.     

Topographic organization of the ventral striatal efferent projections in the rhesus monkey: An anterograde tracing study

The ventral striatum is considered to be that portion of the striatum associated with the limbic system by virtue of its afferent connections from allocortical and mesolimbic areas as well as from the amygdala. The efferent projections from this striatal region in the primate were traced by using 3H aminoacids and Phaseolus vulgaris-leucoagglutinin (PHA-L). Particular attention was paid to the topographic organization of terminal fields in the globus pallidus and substantia nigra, the projections to non-extrapyramidal areas, the relationship between projections from the nucleus accumbens and the other parts of the ventral striatum, and the comparison between ventral and dorsal striatal projections. This study demonstrates that in monkeys a circumscribed region of the globus pallidus receives topographically organized efferent fibers from the ventral striatum. The ventral striatal fibers terminate in the ventral pallidum, the subcommissural part of the globus pallidus, the rostral pole of the external segment, and the rostromedial portion of the internal segment. The more central and caudal portions of the globus pallidus do not receive this input. This striatal output appears to remain segregated from the dorsal striatal efferent projections to pallidal structures. Fibers from the ventral striatum projecting to the substantia nigra are not as confined to a specific region as those projecting to the globus pallidus. Although the densest terminal fields occur in the medial portion, numerous fibers also extend laterally to innervate the dorsal stratum of dopaminergic neurons of the substantia nigra and the retrorubral area. Furthermore, they project throughout the rostral-caudal extent of the substantia nigra. Projections from the medial part of the ventral striatum reach the more caudally located pedunculopontine tegmental nucleus. Thus unlike the above described terminals in the globus pallidus, the ventral striatum project widely throughout the substantia nigra, a fact that indicates that they may contribute to the integration between limbic and other output systems of the striatum. Finally, the ventral striatum projects to non-extrapyramidal regions including the bed nucleus of the stria terminals, the nucleus basalis magnocellularis, the lateral hypothalamus, and the medial thalamus.     

Synaptic inputs of neuropeptide Y-immunoreactive noradrenergic nerve terminals to neurons in the nucleus preopticus medianus which project to the paraventricular nucleus of the hypothalamus of the rat: a combined immunohistochemical and retrograde tracing method

The nucleus preopticus medianus (POMe) is known to serve as a relay site in the neural pathway, from the subfornical organ to the paraventricular nucleus of the hypothalamus (PVN), and to play an important role in the regulation of fluid balance and caridovascular control. A neural connection of noradrenergic nerve terminals in the POMe was examined using electron microscopic immunohistochemistry with the retrograde tract tracing method. Double immunofluorescent labelling revealed nerve terminals immunoreactive to both tyrosine hydroxylase (TH) and neuropeptide Y (NPY) and those immunoreactive to both TH and noradrenaline in the POMe. This indicates that there is an NPY-immunoreactive noradrenergic innervation in the POMe. At the electron microscopic level, nerve terminals immunoreactive to TH or NPY in the POMe formed synapses with dendrites or cell bodies of neurons which were retrogradely labeled after injection of the retrograde tracer, WGA-HRP-colloidal gold, in the PVN. These observations suggest that neurons in the POMe with projections to the PVN may be directly affected by NPY-immunoreactive noradrenergic afferent fibers which presumably originate in the brainstem.