Localization and developmental pattern of vasoactive intestinal polypeptide binding sites in the human hypothalamus

Using a quantitative in vitro autoradiographic approach, vasoactive intestinal polypeptide (VIP) binding site densities were compared in the post-mortem hypothalamus of human neonate/infant and adult. The densities were similar during development in most of the hypothalamic nuclei and areas examined underlying the stability of ¹²⁵I-VIP binding sites in the post-mortem hypothalamus of young and adult individuals. However, the ventral part of the medial preoptic area, the medial, lateral, and supramammillary nuclei were characterized by an increase of ¹²⁵I-VIP binding with age. In young and adult individuals, the highest densities of hypothalamic ¹²⁵1-VIP binding sites were detected in the supraoptic and infundibular nuclei; the ependyma; the organum vasculosum of the lamina terminalis; the horizontal limb of the diagonal band of Broca; the ventral part of the medial preoptic area (in adult); the suprachiasmatic, paraventricular, and periventricular nuclei; and the medial and lateral mammillary nuclei in adult. Moderate densities were found in the vertical limb of the diagonal band of Broca, the bed nucleus of the stria terminalis, the ventral part of the medial preoptic area in neonate/infant, the medial and lateral mammillary nuclei in neonate/infant, the supramammillary nucleus in adult, the dorsal hypothalamic area, and the ventromedial nucleus. Low to moderate binding site densities were observed in the other hypothalamic regions of young or adult individuals. The nonspecific binding ranged from 15% of the total binding in the anterior hypothalamus to 20% in the mediobasal and posterior hypothalamic levels. Taken together, these results provide evidence for a large distribution of VIP binding sites in neonate/infant and adult human hypothalamus suggesting the implication of VIP in the development of this brain structure and the maintenance of its various functions. © 1994 Wiley-Liss, Inc.     

Efferents of the medial preoptic area in the guinea pig: An autoradiographic study

Medial preoptic axons were traced into the diagonal band of Broca and septum, particularly lateral septum. Other labeled fibers could be followed dorsally from medial preoptic area injections adjacent to the stria medullaris, and in the periventricular fiber system and the stria terminalis and its bed nucleus. The anterior and medial amygdaloid nuclei were labeled by fibers via the stria terminalis and others arching over the optic tract and through the substantia innominata. The lateral habenula was labeled. Labeled periventricular fibers reached the periventricular nucleus of the thalamus. Descending efferents were traced principally below the fornix and in the adjacent lateral hypothalamus to label the anterior hypothalamus, the tuberal nuclei, and median eminence. Axons of the medial preoptic area joined the medial part of the medial forebrain bundle and distributed to the reticular formation and the central gray of the midbrain and pons. A small amount of contralateral connections were described.     

Benzodiazepine binding sites in the human hypothalamus. Autoradiographic study

Using in vitro labelling and autoradiographic techniques, we have analyzed the fine and the detailed distribution of benzodiazepine binding sites in the post-mortem human hypothalamus. Binding sites were labelled in mounted tissue sections from adult brains, using the selective high affinity ligand [3H]-Flunitrazepam. A heterogeneous distribution of benzodiazepine binding sites was found throughout the rostrocaudal extent of human hypothalamus. The autoradiographic labelling was shown in the three hypothalamic parts, i.e., anterior, mediobasal and posterior levels. At the anterior level, the highest densities were present in the diagonal band of Broca, the preoptic area (medial and lateral parts) and the septohypothalamic nucleus. At the mediobasal hypothalamic level, the highest densities were mainly localized in the ventromedial nucleus, whereas the other structures were moderately labelled with [3H]-Flunitrazepam. The mammillary complex as well as the posterior hypothalamic area represented the most heavily labelled structures in the posterior hypothalamus. The results obtained in this study, indicate the presence of a large and heterogeneous distribution of benzodiazepine binding sites in human adult hypothalamus. This could support their implication in the control of distinct neural functions (like neuroendocrine role).     

Regional distribution of benzodiazepine binding sites in the human newborn and infant hypothalamus. A quantitative autoradiographic study

Using in vitro quantitative autoradiography and [3H]flunitrazepam we examined the rostrocaudal distribution of benzodiazepine binding sites in the human neonate/infant hypothalamus. The autoradiographic analysis shows the presence of a heterogeneous distribution throughout the rostrocaudal extent of this brain structure. High [3H]flunitrazepam binding corresponds primarily to the diagonal band of Broca and the preoptic region. The labelling in the preoptic region showed a rostrocaudal increase, contrasting in that with the other hypothalamic structures. Intermediate densities were present in the septohypothalamic, suprachiasmatic, periventricular and paraventricular nuclei as well as in the mammillary complex. Low binding was observed in the other hypothalamic structures. The benzodiazepine binding sites analyzed belong mostly to type II receptors. In an attempt to unravel possible differences related to age, we compared the autoradiographic distribution in three postnatal age ranges. The topographical distribution of these binding sites was almost identical in each period analyzed. We found, however, that benzodiazepine binding is generally low in the neonatal period and a tendency in increasing densities is observed during development. Taken together, these results provide evidence for a large distribution of benzodiazepine binding sites in neonate/infant hypothalamus, suggesting their implication in the development of this brain structure and the maintenance of its various functions.     

Forebrain afferents to the cat posterior hypothalamus: a double labeling study

Using a double immunostaining technique with cholera toxin (CT) as a retrograde tracer, we examined the cells of origin and the histochemical nature of afferents to the cat posterior hypothalamus. After injection in the tuberomamillary nucleus, a number of CT-labeled cells were observed in: medial preoptic area, nuclei of the septum and the stria terminalis, amygdaloid complex, anterior hypothalamic, ventromedial hypothalamic and premamillary nuclei. CT injections in the lateral hypothalamic area gave an additional heavy labeling of neurons in: lateral preoptic area, nuclei of the diagonal band of Broca, substantia innominata, and nucleus accumbens. The posterior hypothalamus receives: 1) cholinergic inputs from the septum, the lateral preoptic area and the nuclei of the diagonal band of Broca; 2) dopaminergic afferents from A11, A13, and A14 groups; 3) histaminergic afferents from the posterior hypothalamus; and 4) peptidergic afferents such as methionin-enkephalin, galanin and neurotensin, substance P and corticotropin-releasing factor from the medial preoptic area, the nucleus of the stria terminalis and/or the posterior hypothalamic structures.     

Localisation of mRNA encoding the protein precursor of galanin in the monkey hypothalamus and basal forebrain

The hypothalamic and basal forebrain sites of synthesis of preprogalanin mRNA were identified in three adult monkeys (Macaca fascicularis) by in situ hybridisation performed with a radiolabelled cRNA probe transcribed from human preprogalanin cDNA. With stringent hybridisation conditions, the cRNA probe was hybridised to free-floating sections containing structures contiguous with the rostral hypothalamus through to the caudal limit of the hypothalamus as defined by the mammillary bodies. Specific hybridisation of the preprogalanin cRNA probe occurred throughout the hypothalamus but was particularly intense in the arcuate, paraventricular (parvicellular and magnocellular portions), and dorsomedial nuclei. Moderate hybridisation was found in the periventricular nucleus and scattered hybridisation in the medial preoptic nucleus. The medial preoptic area and the anterior and lateral hypothalmic areas showed moderate to intense hybridisation in scattered cells. A few cells in the tuberal portion and dorsal cap of the anterior portion of the supraoptic nucleus were labelled. Isolated cells were also labelled in the zona incerta. There was little labelling in the dorsal hypothalamic area but moderate labelling in the posterior hypothalamic area. Structures contiguous with the rostral hypothalamus including the diagonal band of Broca, bed nucleus of stria terminalis, substantia innominata, and basal nucleus of Meynert showed intense hybridisation. These data indicate a widespread distribution of preprogalanin mRNA in the monkey hypothalamus. A comparison with the previously reported distribution of preprogalanin mRNA in the rat, as well as with the distribution of galanin-like immunoreactivity in the rat and human, suggests some important species differences. Of particular interest were differences in the supraoptic, suprachiasmatic, and dorsomedial nuclei. The intense hybridisation throughout the paraventricular nucleus and in the rostral arcuate nucleus suggests that galanin may play a role in the regulation of both posterior and anterior pituitary function. © 1993 Wiley-Liss, Inc.     

Autoradiographic localization of thyrotropin-releasing hormone receptors in the rat central nervous system

We employed quantitative autoradiography to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat CNS. The binding of [3H]3-methyl-histidine-TRH [( 3H]MeTRH) to TRH receptors in frozen rat brain sections was saturable, of a high affinity (Kd = 5 nM), and specific for TRH analogs. Autoradiograms of [3H]MeTRH binding showed highest concentrations of TRH receptors in the rhinencephalon, including accessory olfactory bulb, nuclei of the amygdala, and the ventral dentate gyrus and subiculum of the hippocampus. Moderate TRH receptor concentrations were found within the thalamus and hypothalamus, in most regions of the rhombencephalon, such as the cranial nerve nuclei, and in the substantia gelatinosa of the spinal cord. Neocortex and basal ganglia contained low densities of TRH receptors. This distribution correlates well with the sensitivity of brain regions to the known effects of TRH, and suggests that TRH receptors may mediate the actions of TRH in the rat CNS.     

Retrograde double-labeling study of common afferent projections to the dorsal raphe and the nuclear core of the locus coeruleus in the rat

Common afferent projections to the dorsal raphe (DR) and locus coeruleus (LC) nuclei were analyzed in the rat by making paired injections of retrograde tracers, gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) and Fluorogold (FG), into the DR and the nuclear core of the LC. Our results demonstrate that the largest number of double-labeled neurons was located at various preoptic regions including medial preoptic area, lateral preoptic nucleus, and ventrolateral preoptic nucleus. The majority of labeled cells were also observed at the lateral hypothalamus, where the number of labeled cells was comparable to that of neurons at the medial preoptic area or lateral preoptic nucleus. A few double-labeled cells were observed at various hypothalamic regions including anterior, medial tuberal, posterior, and arcuate nuclei, as well as mesencephalic areas including substantia nigra compacta and ventrolateral/lateral periaqueductal gray matter. Cells were also observed at prelimbic/infralimbic prefrontal cortices, diagonal band of Broca, bed nucleus of stria terminalis, and pontine/medullary regions including various raphe nuclei, Barrington's nucleus, gigantocellularis, paragigantocellularis, prepositus hypoglossi, subcoeruleus, and dorsomedial tegmental area. Although electrophysiological studies need to be performed, a large number of double-labeled neurons located at preoptic regions as well as lateral hypothalamus might have their major role in simultaneous control over these monoaminergic nuclei as a means of influencing various sleep and arousal states of the animal. Double-labeled cells at the other locations might be positioned to influence a variety of other functions such as analgesia, cognition, and stress responses.     

Immunohistochemical distribution of somatostatin in the infant hypothalamus

Somatostatin (SS)-containing neurons were mapped in the normal infant hypothalamus with immunohistochemistry, using the peroxidase anti-peroxidase technique. Neurons displaying SS immunoreactivity show a widespread distribution throughout the hypothalamic region. Principal SS-immunoreactive like (SS-IL) perikarya are located in the paraventricular, infundibular and posterior nuclei and in the preoptic region. High SS innervation is also found in the ventromedial and in the lateral mammillary nuclei, and in the median eminence. In general this distribution of SS-IL agrees well with that reported for rat. Compared to the immunohistochemical distribution of SS in human adult hypothalamus, this mapping in the infant hypothalamus is grossly similar. However some differences may be underlined: the presence of a moderately dense group of SS-IL perikarya in the tuberal and posterior nuclei, and a dense innervation of the ventromedial nucleus and in the median eminence. This first detailed distribution of SS immunoreactivity in infant hypothalamus can provide basic knowledge for further studies of infant neuropathology.     

Thyrotropin-releasing hormone immunoreactivity in the brain and the pituitary during Bufo arenarum development.

The ontogeny of the thyrotropin releasing hormone (TRH) neuronal system was evaluated by immunocytochemistry in Bufo arenarum. The first appearance of TRH immunoreactive fibers was at early premetamorphosis. These fibers were found in small numbers and weakly stained in the median eminence and pars nervosa. With the advance of larval development, TRH-like material stained intensely and tended to aggregate in the median eminence, pars nervosa and pars intermedia. At climax stages immunoreactive fibers and perikarya (weakly stained) were also identified in the preoptic area. In adult specimens TRH perikarya and neuronal fibers were found in the preoptic and infundibular nuclei of the hypothalamus and in the amygdala, septum and diagonal band of Broca of the telencephalon. In addition, TRH neuronal fibers and endings were found in the preoptic-hypophyseal tract, the external zone of the median eminence, the pars nervosa and pars intermedia. Fibers were absent in the pars distalis. This study represents the first immunocytochemical demonstration of TRH in Bufo species, and serves as a basis for clarification of the neuroendocrine regulation of metamorphosis.     

Efferent projections from the region of the medial zona incerta containing A13 dopaminergic neurons: a PHA-L anterograde tract-tracing study in the rat

Potential efferent projections of A₁₃ dopaminergic (DA) neurons were identified in the present study by examining the distribution of labelled fibers following iontophoretic injection of the anterogradely transported lectinPhaseolus vulgaris leucoagglutinin (PHA-L) into the medial zona incerta (MZI), the region of the diencephalon containing A₁₃ DA neuronal perikarya. One week after injection, PHA-L labelled fibers were found throughout the brain with the heaviest labelling occurring ipsilateral to the injection site in the anterior hypothalamic area, lateral hypothalamus, lateral preoptic area, horizontal diagonal band of Broca, and parvocellular region of the paraventricular nucleus. Moderate labelling was observed in the ipsilateral median preoptic nucleus, lateral septum, lateral aspect of the bed nucleus of the stria terminalis, and central nucleus of the amygdala. Moderate labelling was also found in the contralateral MZI and parvocellular region of the paraventricular nucleus. Light labelling was detected in the ipsilateral medial preoptic area, supraoptic nucleus, ventromedial nucleus, arcuate nucleus, vertical limb of the diagonal band of Broca, and in the contralateral lateral hypothalamus. Few immunopositive fibers were present in the dorsomedial nucleus of the hypothalamus or the magnocellular region of the paraventricular nucleus. These results reveal that neurons located in the MZI (possibly A₁₃ DA neurons) have ipsilateral efferent axonal projections to a variety of brain regions including the lateral hypothalamus, lateral preoptic area, and the limbic structures at the diencephalic-telencephalic juncture.     

Thyrotropin-releasing hormone immunoreactivity in the brain and the pituitary during Bufo arenarum development

The ontogeny of the thyrotropin releasing hormone (TRH) neuronal system was evaluated by immunocytochemistry in Bufo arenarum. The first appearance of TRH immunoreactive fibers was at early premetamorphosis. These fibers were found in small numbers and weakly stained in the median eminence and pars nervosa. With the advance of larval development, TRH-like material stained intensely and tended to aggregate in the median eminence, pars nervosa and pars intermedia. At climax stages immunoreactive fibers and perikarya (weakly stained) were also identified in the preoptic area. In adult specimens TRH perikarya and neuronal fibers were found in the preoptic and infundibular nuclei of the hypothalamus and in the amygdala, septum and diagonal band of Broca of the telencephalon. In addition, TRH neuronal fibers and endings were found in the preoptic-hypophyseal tract, the external zone of the median eminence, the pars nervosa and pars intermedia. Fibers were absent in the pars distalis. This study represents the first immunocytochemical demonstration of TRH in Bufo species, and serves as a basis for clarification of the neuroendocrine regulation of metamorphosis.     

Efferent projections from the lateral hypothalamus in the guinea pig: An autoradiographic study

Autoradiography was employed to investigate the efferent projections from the lateral hypothalamus in the guinea pig. Lateral hypothalamic axons were traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced to the lateral preoptic area, diagonal band of Broca, and septal nuclei. Posterior projections included the ventral tegmental area of Tsai, central gray matter and the reticular formation throughout the brain stem. Laterally, the lateral hypothalamic efferents were found in the stria terminalis, amygdala and globus pallidus. Dorsally, the lateral hypothalamic axons projected to the midline nuclei of the thalamus and bilaterally to the lateral habenular nuclei. Projections to the medial hypothalamus included a labeled fiber bundle to the internal layer of the median eminence and to the posterior lobe of the pituitary gland. Labeled fibers and diffuse label were also found in some areas contralateral to the injection site.     

Topography and associations of luteinizing hormone-releasing hormone and neuropeptide Y-immunoreactive neuronal systems in the human diencephalon

Neuropeptide Y (NPY) potentiates the effect of luteinizing hormone-releasing hormone (LHRH) on luteinizing hormone secretion in several species, including human. In addition to the pituitary sites, the interactions of the NPY and LHRH systems may involve diencephalic loci. However, the morphologic basis of this putative communication has not yet been elucidated in the human brain. To discover interaction sites, the distribution and connections of LHRH and NPY-immunoreactive (IR) neuronal elements in the human hypothalamus were investigated by means of light microscopic single- and double-label immunocytochemistry. NPY-IR perikarya and fibers were found to be widely distributed in the ventral diencephalon, with high densities in the preopticoseptal, periventricular, and tuberal regions. Small neuronal cell groups were infiltrated with a dense network of varicose NPY-IR fibers in the lateral preoptic area. The LHRH-IR perikarya were located mainly in the preopticoseptal region, diagonal band of Broca, lamina terminalis, and periventricular and infundibular nuclei. A few LHRH-IR neurons and fibers were scattered in the mamillary region. The overlap between the NPY and LHRH systems was apparent in the periventricular, paraventricular, and infundibular nuclei. Double-labeling immunohistochemistry showed NPY-IR axon varicosities in contact with LHRH-IR perikarya and main dendrites. The putative innervation of LHRH neurons by NPY-IR fibers was also seen in 1-microm-thick plastic sections and with confocal laser scanning microscope, thus further supporting the functional impact of NPY-IR terminals on LHRH-IR neurons. The present findings suggest that the hypophysiotropic LHRH-synthesizing neurons may be innervated by intrahypothalamic NPY-IR fibers. Confirmation by ultrastructural analysis would demonstrate that the LHRH system in the human hypothalamus is regulated by NPY, as has been demonstrated in nonhuman species.     

Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study

Sites which bind oxytocin and vasopressin with high affinity were detected in the brain and upper spinal cord of 12 human subjects, using in vitro light microscopic autoradiography. Tissue sections were incubated with tritiated vasopressin, tritiated oxytocin or an iodinated oxytocin antagonist. The ligand specificity of binding was assessed with unlabelled vasopressin or oxytocin in excess, as well as in competition experiments using synthetic structural analogues. The distribution of vasopressin binding sites differed markedly from that of oxytocin binding sites in the forebrain, while there was overlap in the brainstem. Vasopressin binding sites were detected in the dorsal part of the lateral septal nucleus, in midline nuclei and adjacent intralaminar nuclei of the thalamus, in the hilus of the dentate gyrus, the dorsolateral part of the basal amygdaloid nucleus and the brainstem. The distribution of oxytocin binding sites in the brainstem has been recently reported (Loup et al., 1989). Oxytocin binding sites were also observed in the basal nucleus of Meynert, the nucleus of the vertical limb of the diagonal band of Broca, the ventral part of the lateral septal nucleus, the preoptic/anterior hypothalamic area, the posterior hypothalamic area, and variably in the globus pallidus and ventral pallidum. The presence of oxytocin and vasopressin binding sites in limbic and autonomic areas suggests a neurotransmitter or neuromodulator role for these peptides in the human central nervous system. They may also affect cholinergic transmission in the basal forebrain and consequently play a role in Alzheimer's disease.     

Previous maternal experience potentiates the effect of parturition on oxytocin receptor mRNA expression in the paraventricular nucleus

In sheep, central oxytocin release at parturition induces maternal behaviour which is thought to be mediated by changes in the expression of central oxytocin receptors. The distribution, effects of parturition, previous maternal experience and hormonal status on the distribution of an oxytocin receptor was investigated using immunocytochemistry and in situ hybridization. In ewes with no previous maternal experience, parturition induced significant increases in oxytocin receptor mRNA expression in the anterior olfactory nucleus, medial preoptic area, ventromedial hypothalamus, lateral septum, medial amygdala, bed nucleus of the stria terminalis and diagonal band of Broca. In maternally experienced ewes, parturition induced additional increases in two areas, the paraventricular nucleus and the Islands of Calleja. The changes in progesterone and oestrogen that occur during late pregnancy and parturition appear to contribute to increases in expression in the anterior olfactory nucleus, Islands of Calleja, medial preoptic area, ventromedial hypothalamus, bed nucleus of the stria terminalis and diagonal band of Broca, but not in the paraventricular nucleus, lateral septum and medial amygdala. These results demonstrate that progesterone and oestrogen priming enhance oxytocin receptor mRNA expression in a number of regions in the olfactory system, hypothalamus and limbic brain. These effects appear to be independent of maternal experience. Parturition increases oxytocin receptor mRNA expression in all the areas influenced by hormonal priming and the lateral septum, medial amygdala and paraventricular nucleus. Maternal experience also enhances expression of oxytocin receptor mRNA in the paraventricular nucleus and the Islands of Calleja. Because the paraventricular nucleus is the main source of oxytocin release in the brain, this upgrading of autoreceptors as a result of maternal experience may serve to enhance release of this peptide in projection sites regulating maternal behaviour.     

Properties of [3H](3-Me-His2)TRH binding to apparent TRH receptors in the sheep central nervous system

[3H](3-methyl-His2)thyrotropin releasing hormone ([3H]MeTRH) binds to sites in the sheep central nervous system (CNS) whose properties closely resemble both those of CNS binding sites for [3H]TRH and those of pituitary binding sites for [3H]MeTRH. Detailed studies for binding of [3H]MeTRH in the sheep nucleus accumbens and retina have yielded equilibrium dissociation constants of about 4 nM and densities of binding sites of about 3 and 2 pmol/g wet weight, respectively. The binding affinity of [3H]MeTRH was 8- to 10-fold higher than that of [3H]TRH, resulting in much lower non-specific binding with the new ligand. The association reaction had a rate constant of about 2-3 x 10(7) M-1 min-1, while the biphasic dissociation reaction had rate constants of 8-9 x 10(-2) min-1 for the fast phase and 1-2 x 10(-2) min-1 for the slow phase. The regional distribution of binding in the sheep CNS was similar to that observed previously with [3H]TRH. Highest binding outside the pituitary was in the nucleus accumbens area and retina, with another peak in the amygdala-temporal cortex area. Binding was widely distributed, so that no CNS region appeared totally devoid of binding. Nineteen TRH analogs, ranging in potency over 6 orders of magnitude, showed nearly identical abilities to complete for binding of [3H]MeTRH in the CNS areas and in the sheep anterior pituitary gland in side-by-side experiments. These findings argue strongly for identification of [3H]MeTRH binding sites in the CNS as TRH receptors.     

Efferents from medial basal forebrain and hypothalamus in the rat. I. An autoradiographic study of the medial preoptic area.

Efferent projections from the medial and periventricular preoptic area, bed nucleus of the stria terminalis and nuclei of the diagonal band were traced using tritiated amino acid autoradiography in albino rats. Medial and periventricular preoptic area efferents were not restricted to short-axon projections. Ascending projections from the medial preoptic area (mPOA) were traced through the diagonal band into the septum. Descending mPOA axons coursed in the medial parts of the medial forebrain bundle. Projections to most hypothalamic nuclei, including the arcuate nucleus and median eminence, were observed. In the midbrain, mPOA efferents were distributed in the central grey, raphe nuclei, ventral tegmental area and reticular formation. Projections from the mPOA were also observed to the amygdala through the stria terminalis, to the lateral habenula through the stria medullaris, and to the periventricular thalamus. Axons of the most medial and periventricular preoptic area (pvPOA) neurons had a distribution similar to more lateral mPOA neurons but their longest-axoned projections were weaker. The pvPOA did not send axons through the stria medullaris but did project more heavily than the more lateral mPOA to the arcuate nucleus and median eminence. Projections from the bed nucleus of the stria terminalis (nST) were in most respects similar to those from the medial preoptic area, with the major addition of a projection to the accessory olfactory bulb. The nuclei of the diagonal band of Broca (nDBB) gave a different pattern of projections than mPOA or nST, projecting, for instance, to the medial septum and hippocampus. Descending nDBB efferents ran in the ventral portion of the medial forebrain bundle. Among hypothalamic cell groups, only the medial mammillary nuclei received nDBB projections. nDBB efferents also distributed in the medial and lateral habenular nuclei and the mediodorsal thalamic nucleus.     

The habenula as an evolutionary conserved link between basal ganglia,limbic, and sensory systems—A phylogenetic comparison based on anuran amphibians

Based on anatomical and functional data, the habenula—a phylogenetically old brain structure present in all vertebrates—takes part in the integration of limbic, sensory, and basal ganglia information to guide effective response strategies appropriate to environmental conditions. In the present study, we investigated the connections of the habenular nuclei of the oriental fire-bellied toad, Bombina orientalis, and compared them with published data from lampreys, chondrichthyes, teleosts, reptiles, birds, and mammals. During phylogenetic development, the primordial habenula circuitry underwent various evolutionary adaptations and in the tetrapod line, the circuit complexity increased. The habenula circuitry of anuran amphibians, decedents of the first land-living tetrapods, seem to exhibit a mix of ancient as well as modern features. The anuran medial and lateral habenula homologs receive differential input from the septum, nucleus of the diagonal band of Broca, preoptic area, hypothalamus, rostral pallium, nucleus accumbens, ventral pallidum, and bed nucleus of the stria terminalis. Additional input arises from a border region in the ventral prethalamus, here discussed as a putative homolog of the entopeduncular nucleus of rodents. The habenular subnuclei also differentially innervate the interpeduncular nucleus, raphe nuclei, substantia nigra pars compacta and ventral tegmental area homologs, superficial mamillary area, laterodorsal tegmental nucleus, locus coeruleus, inferior and superior colliculus homologs, hypothalamus, preoptic area, septum, nucleus of the diagonal band of Broca, and main olfactory bulb. It seems likely that the main connectivity between the habenula and the basal ganglia, limbic, and sensory systems was already present in the common tetrapod ancestor.     

An analysis of the efferent connections of the septal area in the cat

The neuroanatomical organization of the efferent connections of the septal area in the cat was analyzed by the use of anterograde ([3H]leucine radioautography) and retrograde (horseradish peroxidase histochemistry) tracing techniques. The results indicate that the lateral septal nucleus projects to the nuclei of the diagonal band, preoptic area, lateral hypothalamus, and supramammillary region. The projections of the septofimbrial nucleus supply the nuclei of the diagonal band and the medial habenular nucleus. Projection targets of the vertical limb of the diagonal band are widespread and include the preoptic area, lateral hypothalamus, anterior limbic cortex, amygdala, medial habenular nucleus, interpeduncular nucleus and hippocampal formation. The projection from the vertical limb to the hippocampal formation is organized in a topographical manner in such a fashion that cells positioned near the midline project to the dorsal hippocampus and adjoining subicular cortex while fibers originating from cells situated more laterally project to more ventral parts of the hippocampal formation. In general, the projections from the horizontal limb were similar to those from the vertical limb, but several differences were noted. Fibers arising from the horizontal limb are distributed to the ventral tegmental area and interpeduncular nucleus but this region seems to lack a projection to either the habenular complex or to the ventral aspect of the hippocampal formation. Fibers arising from the bed nucleus of the anterior commissure are distributed to the preoptic region, lateral hypothalamus, supramammillary region, posterior aspect of the medial mammillary nucleus and lateral habenular nucleus.