Supramammillary Nucleus Research Articles

Medial forebrain bundle of the rat: IV. Cytoarchitecture of the caudal (lateral hypothalamic) part of the medial forebrain bundle bed nucleus

In the preceding study (Geeraedts et al.: J. Comp. Neurol. 294:507-536, '90), the rostral or telencephalic portion of the rat's bed nucleus of the medial forebrain bundle (MFB) has been parcellated into several cytoarchitectonically distinct cellular groups and subgroups. The purpose of the present investigation is to subject the caudal or lateral hypothalamic (LH) portion of the MFB bed nucleus to a detailed cytoarchitectonic analysis. This analysis is based on the same materials, methods, and cytoarchitectonic criteria that were also employed in the preceding study. In contrast to descriptions in the literature, it was found that the LH-region constitutes a very heterogeneous population of neurons with an evident arrangement into groups, several of which have not been identified previously. Many of these cellular groups are partly or entirely located within the boundary of the LH-trajectory of the MFB as previously established by Nieuwenhuys et al. (J. Comp. Neurol. 206:49-81, '82). These groups are designated here as the MFB-related cellular groups. They appear to be arranged into two longitudinal zones. Both zones are caudally replaced by the ventral tegmental area (VTA) and a part of the mesencephalic tegmentum (TEGM1). The lateral zone lies in close proximity to the internal capsule/cerebral peduncle and comprises the following cellular groups: the ventrolateral subarea of the lateral hypothalamic area (LHVL), the anterolateral subarea of the lateral hypothalamic area (LHAL), the lateral tuberal nucleus (TUL), the pre-subthalamic nucleus (PSUT), the retro-subthalamic nucleus (RSUT), the anterodorsal subarea of the lateral hypothalamic area (LHAD), and the lateral hypothalamic nucleus (LHN). The medial zone consists of the following cellular groups: the intermediate hypothalamic area (IHA), the medial tuberal nucleus (TUM), the perifornical nucleus (PFX), the lateral supramammillary nucleus (SUL), the submammillothalamic nucleus (SMT), and the nucleus geminus posterior (GEP). The cellular groups of the medial zone together with the tuberomammillary nucleus groups of the medial zone together with the tuberomammillary nucleus (TUMM) are positioned at the interface between the lateral and the medial hypothalamus, and form an array of cellular groups indicated in our study as the intermediate division of the hypothalamus. The MFB-related cellular groups are dorsally, medially, ventrally, and laterally surrounded by rather well-known brain structures. Both the MFB-related cellular groups and the surrounding structures have been identified and delimited. This resulted in a new, elaborate cytoarchitectonic atlas of the rat's lateral hypothalamic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329

In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity.

Immunohistochemistry of endogenous l-DOPA in the rat posterior hypothalamus

The aim of this work was to study L-DOPA-containing neuronal structures of the rat posterior and dorsal hypothalamus by means of immunohistochemistry using antiserum against glutaraldehyde conjugated L-DOPA. Aspects and distribution of L-DOPA immunoreaction among cells of the supramammillary nucleus and the A11, A13c and A13 cell groups are described and compared to dopamine immunoreactivity, mainly through a double colored labelling procedure employing a color modification of the DAB reaction by metallic ions. Differences between L-DOPA and dopamine stainings within cell groups as the presence of cells with predominant or exclusive L-DOPA coloration are tentatively explained under the light of previous findings using immunohistochemistry of catecholamines synthesizing enzymes and catecholamines histofluorescence.

Afferents to the median raphe nucleus of the rat: Retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selective d-[ 3H]aspartate labelling of possible excitatory amino acid inputs

Afferents to the median-paramedian raphe nuclear complex, which contains the B8 serotonergic cell group, were investigated in the rat with neuroanatomical and transmitter-selective retrograde labelling techniques. Injection of sensitive retrograde tracers, cholera toxin genoid or wheat germ agglutinin conjugated horseradish peroxidase into the median raphe resulted in labelling of neurons in a large number of brain regions. Projections from 26 of these regions are supported by available orthograde tracing data; the cingulate cortex, bed nucleus of stria terminalis, medial septum and diagonal band of Broca, ventral pallidum, medial and lateral preoptic areas, lateral hypothalamus, dorsomedial nucleus of hypothalamus, lateral habenula, interpeduncular nucleus, substantia nigra, central (periaque-ductal) gray, and laterodorsal tegmental nucleus seem to represent major sources of afferents to the median-paramedian raphe complex. Retrogradely labelled cells were also observed in a number of regions for which anterograde tracing data are not available, including the perifomical hypothalamic nucleus, ventral premammillary nucleus, supramammillary and submammillothalamic nuclei and the B9 area. Possible excitatory amino acid afferents were identified with retrograde d-[ 3H]aspartate labelling. Microinjection of d-[ 3H]aspartate at a low concentration, 10 −4 M in 50 nl, resulted in retrograde labelling of a limited number of median raphe afferents. The most prominent labelling was observed in the lateral habenula and the interpeduncular nucleus, but retrogradely labelled cells were also noted in the medial and lateral preoptic areas, lateral and dorsal hypothalamus, ventral tegmental area, laterodorsal tegmental nucleus, medial parabrachial nucleus, and the pontine tegmentum. After injections of 10 −3 M d-[ 3H]aspartate selective labelling also appeared in more distant afferent regions, including cells in cingulate cortex, and in some regions located at shorter distances, such as the supramammillary nucleus. Injections of d-[ 3H]aspartate at high concentration, 10 −2M, resulted in the appearance of weakly to moderately labelled cells in most afferent areas which were devoid of labelled cells after injections of lower concentrations, suggesting that this labelling may be non-specific. It was concluded that the median-paramedian raphe receives afferents from a large number of forebrain and hypothalamic regions, while relatively few brain stem regions project to this nuclear complex. The selectivity of retrograde labelling with d-[ 3H]aspartate was found to be concentration dependent, and it is suggested that the connections showing high affinity for d-[ 3H]aspartate may use excitatory amino acids as transmitters. Excitatory amino acid inputs from lateral habenula and interpeduncular nucleus may play predominant roles in the control of ascending serotonergic and non-serotonergic projections originating in the median and paramedian raphe nuclei.

Neurons containing cholecystokinin mRNA in the mammillary region: ontogeny and adult distribution in the rat.

1. The ontogeny and adult distribution of neurons containing cholecystokinin (CCK) mRNA in the premammillary and mammillary nuclei and supramammillary region of the rat brain were studied using hybridization histochemistry. 2. The earliest detection of CCK mRNA in the mammillary region was on E14, followed by a marked increase in transcript levels during the next 4 days, a time during which neurons in this region still divide. During the first 2 weeks of life, few changes in the levels of CCK transcripts were seen, and an adult-like pattern of expression was seen on the twenty-first day of life. 3. Low levels of transcripts were present in numerous neurons located in all divisions of the medial nucleus and in the posterior nucleus known to project ipsilaterally to the anteroventral and anteromedial thalamic nuclei. In contrast, none of the neurons in the lateral nucleus (projecting bilaterally to the anterodorsal thalamic nucleus) had detectable transcripts. 4. Many neurons in the supramammillary nucleus had low, moderate, or high levels of transcripts. Some nearby nuclei (such as the dorsal premammillary nucleus) had smaller numbers of neurons with low levels of CCK mRNA, whereas others (such as the ventral premammillary nucleus) had none.

Substance P-like immunoreactive projection to the hippocampal formation from the posterior hypothalamus in the cat

Following the injection of the fluorescent tracer, 4′,6-diamidino-2-phenylindol-2HCl (DAPI) or Fluoro-Gold (FG), into the hippocampal formation of the cat, retrogradely-labeled cells were seen mainly in the supramammillary nucleus and the posterior hypothalamic area. Some of these labeled cells contain substance P-like immunoreactivity (SP-LI). When wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into the supramammillary nucleus and its adjacent regions, anterogradely-labeled terminals were detected, for the most part, in the granular layer and the supragranular molecular layer of the dentate gyrus as well as in the pyramidal layers of the hippocampus and subiculum. All of these layers were included within the terminal areas containing the SP-like immunoreactivity.

A comparison of supramammillary and medial septal influences on hippocampal field potentials and single-unit activity

1. A comparison was made between the influences of supramammillary (SUM) and medial septal (MS) nuclei on hippocampal physiology in Nembutal-anesthetized rats. Specifically, the effects of prestimulation of the SUM or MS on the perforant path-dentate field potential, on spontaneous activity of single units, and on perforant path-induced unit activation were assessed. Another series of experiments addressed the issue of whether the SUM and MS effects on the perforant path-dentate field response are independent. 2. Prestimulation of the SUM or MS significantly facilitated the perforant path-dentate population spike with no clear effect on the field excitatory postsynaptic potential (EPSP) recorded in the subgranular zone of the dentate hilus. Prestimulation of either nucleus also reduced the threshold for spike onset. The major differences between the two spike facilitation effects were the magnitude of the change and possibly the optimal interstimulus intervals required to obtain the effects. 3. Acute transection of the ipsilateral column of fornix or dorsal fornix eliminated the SUM population spike facilitation effect. MS lesion or dorsal fornix/fimbria transection eliminated the MS spike facilitation effect. The MS lesion did not alter the effects of SUM prestimulation. Cingulum or medial forebrain bundle transection affected neither SUM- nor MS-mediated spike facilitation. Thus the SUM and MS influences on the dentate field response appear to be independent of one another. The relevant SUM afferents travel through the ipsilateral column of fornix and dorsal fornix, whereas MS afferents project through the dorsal fornix/fimbria. 4. Single units recorded in stratum granulosum (SG) were assessed with respect to several parameters. These included the mean firing rate, whether or not excitation occurred prior to the field population spike and at lower threshold, and whether or not a driven unit responded to a second perforant path stimulus delivered at short latency following the first (during the period of population spike depression). The latter parameter in particular appeared to separate SG cells into two classes. The cells that were not activated during the second field potential were classified as granule cells, whereas those that were activated were classified as basket cells. Based on this distinction, significant differences were also found between the two cell classes on the other parameters. In particular, cells classified as granule cells often had very low firing rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat.

Ascending projections from the medial pontine reticular formation, the mesencephalic reticular formation, and the median raphe nucleus were examined using the autoradiographic technique. The majority of the ascending fibers labeled after injections of [3H]-leucine into the nucleus pontis caudalis (RPC) course through the brainstem within the tracts of Forel (tractus fasciculorum tegmenti of Forel) and directly ventral to them. At the caudal diencephalon, Forel's bundle divides into dorsal and ventral components bound primarily for the dorsal thalamus and the subthalamus, respectively. RPC fibers project to several regions involved in oculomotor/visual functions. These include the abducens nucleus, the intermediate gray layer of the superior colliculus (SCi), the anterior pretectal nucleus (APN), the ventral lateral geniculate nucleus (LGNv), and regions of the central gray directly bordering the oculomotor nucleus, the interstitial nucleus of Cajal, and the nucleus of Darkschewitsch. Few, if any, fibers from RPC (or from nucleus pontis oralis-RPO) terminate within the oculomotor nucleus proper. Other sites receiving heavy projections from the RPC include adjacent regions of the pontomesencephalic reticular formation (RF), the parafascicular (PF) and central lateral (CL) nuclei of the thalamus and the fields of Forel/zona incerta (FF-ZI). RPO fibers also ascend predominantly in Forel's bundle. Other ascending tracts for these fibers are the medial longitudinal fasciculus and the central tegmental tract (CTT). RPO fibers distribute significantly to the same structures of the oculomotor/visual system receiving projections from RPC. The RPO projections to the SCi and the APN are particularly pronounced. RPO fibers terminate heavily in several nuclei located ventrally within the rostral midbrain/caudal diencephalon. These include major dopamine-containing cell groups (the retrorubral nucleus, the ventral tegmental area, and the substantia nigra-pars compacta) as well as the interpeduncular nucleus, the lateral mammillary nucleus, and the supramammillary nucleus. Other prominent targets for RPO fibers include the mesencephalic RF, specific regions of the central gray, the PF, the CL, the paracentral and central medial nuclei of the thalamus, and the FF/ZI. The major bundle of the ascending fibers labeled after injections of the mesencephalic reticular formation (MRF) travels within the CTT in a position just lateral to the central gray, but a significant number of labeled axons also course in Forel's bundle.(ABSTRACT TRUNCATED AT 400 WORDS)

Direct projections of non-pyramidal neurons of Ammon's horn to the supramammillary region in the cat

Non-pyramidal neurons in cat Ammon's horn were shown to send their axons to the supramammillary regions (SMR), i.e. the supramammillary nucleus and its vicinities including the supramammillary nucleus and the lateral, posterior and dorsal hypothalamic areas: wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injection into Ammon's horn resulted in labeling of presumed axon terminals in the SMR; and after injecting HRP into the SMR, retrogradely labeled non-pyramidal neurons were seen in Ammon's horn.

The supramammillary region of the cat sends substance P-like immunoreactive axons to the hippocampal formation and the entorhinal cortex

A combined method of the tracing of WGA-HRP (wheat germ agglutinin-conjugated horseradish peroxidase) and the immunohistochemistry of substance P (SP) showed that many SP-like immunoreactive neurons in the supramammillary nucleus of cat hypothalamus sent their axons to the hippocampal formation. SP-like immunoreactive axons in the hippocampal formation and entorhinal cortex were markedly reduced in number ipsilaterally after placing an electrothermic lesion in the supramammillary region of the hypothalamus.

Capsaicin‐induced neuronal degeneration: Silver impregnation of cell bodies, axons, and terminals in the central nervous system of the adult rat

Capsaicin is a neurotoxic substance valued in neurobiological research because of its ability to selectively damage small unmyelinated primary sensory neurons. Previous work has indicated that systemic capsaicin administration causes permanent neuronal degeneration in neonatal rats, but evidence that capsaicin has a similar effect in adults is equivocal and incomplete. Therefore, we used silver impregnation, a method that labels degenerating neurons, to examine the central nervous system of adult rats after systemic capsaicin treatment. Adult rats were injected with a single intraperitoneal dose of capsaicin (50 or 90 mg/kg) or vehicle solution and killed 6, 12, 18, 24, 48, 96, or 240 hours later. Sections of brain and spinal cord were stained with the Carlsen-de Olmos cupric silver method. As reported previously, stained sections revealed degeneration in areas known to be innervated by small-diameter primary sensory fibers: the substantia gelatinosa of the spinal cord dorsal horn and spinal trigeminal nucleus, the solitary nucleus and tract, and the lateral borders of the area postrema. In addition, axon and terminal degeneration was observed in several discrete forebrain and hindbrain areas not previously associated with capsaicin-induced degeneration in either adult or neonatal rats: the inferior olive, the olivary pretectal nucleus, the interpeduncular nucleus, the suprachiasmatic nucleus, and the lateral septum/medial accumbens region. Furthermore, degenerating cell bodies were observed in the intrafascicular nucleus of the ventromedial midbrain tegmentum, in the supramammillary nucleus, and in the posterior hypothalamic area. Unilateral nodose ganglionectomy produced terminal staining on the denervated side very similar to that induced bilaterally by capsaicin. In addition, unilateral nodose ganglionectomy 1 month prior to capsaicin injection greatly attenuated staining in the ipsilateral nucleus of the solitary tract, confirming the hypothesis that capsaicin damages vagal sensory neurons innervating this nucleus. Capsaicin-induced damage in adult rats was long-lasting, since the second of two capsaicin treatments spaced 4.5 months apart produced no additional degeneration.

Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat.

The projections of the medial preoptic nucleus (MPN) were examined by making injections of the anterogradely transported lectin Phaseolus vulgaris leucoagglutinin (PHA-L) into the MPN and charting the distribution of labeled fibers. The evidence indicates that the MPN projects extensively to widely distributed regions in both the forebrain and brainstem, most of which also supply inputs to the nucleus. An important neuroendocrine role for the MPN is underscored by its extensive projections to almost all parts of the periventricular zone of the hypothalamus, including the anteroventral periventricular, anterior part of the periventricular, paraventricular (PVH), and arcuate nuclei, and a role in autonomic mechanisms is indicated by projections to such regions as the dorsal and lateral parvicellular parts of the PVH, the lateral parabrachial nucleus, and the nucleus of the solitary tract. Other projections of the MPN suggest participation in the initiation of specific motivated behaviors. For example, inputs to two nuclei of the medial zone of the hypothalamus, the ventromedial and dorsomedial nuclei, may be related to the control of reproductive and ingestive behaviors, respectively, although the possible functional significance of a strong projection to the ventral premammillary nucleus is presently unclear. The execution of these behaviors may involve activation of somatomotor regions via projections to the substantia innominata, zona incerta, ventral tegmental area, and pedunculopontine nucleus. Similarly, inputs to other regions that project directly to the spinal cord, such as the periaqueductal gray, the laterodorsal tegmental nucleus, certain medullary raphe nuclei, and the magnocellular reticular nucleus may also be involved in modulating somatic and/or autonomic reflexes. Finally, the MPN may influence a wide variety of physiological mechanisms and behaviors through its massive projections to areas like the ventral part of the lateral septal nucleus, the bed nucleus of the stria terminalis, the lateral hypothalamic area, the supramammillary nucleus, and the ventral tegmental area, all of which have extensive connections with regions along the medial forebrain bundle. Although the PHA-L method does not allow a clear demonstration of possible differential projections from each subdivision of the MPN, our results suggest that each of them does give rise to a unique pattern of outputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Brainstem afferents to the basal forebrain in the rat

Brainstem afferents to various nuclei of the basal forebrain of the rat were examined using the retrograde transport of wheat germ agglutinin-horseradish peroxidase. These forebrain nuclei included the medial septum-vertical limb of the diagonal band nucleus, the lateral septum, the nucleus of the horizontal limb of the diagonal band, the medial preoptic area and the magnocellular preoptic nucleus/substantia innominata. Medial septal-vertical limb of the diagonal band injections produced dense cell labeling in: raphe obscurus, nucleus incertus, central gray-pars alpha, locus coeruleus, raphe pontis, median raphe, nucleus of Darkschewitsch, a compact cell group within the mesencephalic gray dorsolateral to the nucleus of Darkschewitsch and the supramammillary nucleus. Lateral septal injections produced the heaviest cell labeling in the A1 and A2 areas (of Dahlstrom and Fuxe), the lateral parabrachial nucleus, the Kolliker-Fuse nucleus, the ventral tegmental area and the supramammillary nucleus. There were considerably fewer labeled cells overall with lateral septal as compared with medial septal injections. Brainstem projections to the horizontal limb of the diagonal band were pronounced. The most heavily labeled nuclei were A1, locus coeruleus, laterodorsalis (dorsolateral tegmental nucleus of Castaldi), raphe pontis, median raphe, lateral parabrachial nucleus, ventral tegmental area, nucleus of Darkschewitsch and the supramammillary nucleus. Medial preoptic area injections produced pronounced labeling in: A1 and A2 areas, raphe magnus, locus coeruleus, laterodorsalis, lateral parabrachial nucleus, pedunculopontine nucleus, peripeduncular nucleus and the supramammillary nucleus. The pattern of brainstem labeling obtained with magnocellular preoptic/substantia innominata injections was considerably different from the patterns seen with the other injections. Specifically, relatively few cell groups, essentially confined to the upper brainstem (rostral pons and midbrain), were densely labeled following magnocellular preoptic/ substantia innominata injections. These included the medial parabrachial nucleus, the pedunculopontine nucleus, the dorsal raphe nucleus, the ventral tegmental area and the supramammillary nucleus. With the exception of the supramammillary nucleus, each of these cell groups was more heavily labeled with magnocellular preoptic/substantia innominata injections than with others of this series. The above describes the major brainstem projections to each of the forebrain sites. Several additional brainstem nuclei sent significant but less pronounced projections to the basal forebrain, such that each forebrain nucleus (with the possible exception of the magnocellular preoptic nucleus/substantia innominata) received afferents from approximately 20–25 brainstem nuclei. The present results indicate a widespread brainstem influence over nuclei of the medial basal forebrain.

Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography

The aim of the present study was to determine the organization of the afferents of the mediodorsal thalamic nucleus in relation to the reciprocal connections of this nucleus with different areas of the prefrontal cortex. For this purpose injections of horseradish peroxidase, or horseradish peroxidase conjugated to wheatgerm agglutinin were placed in different parts of the mediodorsal nucleus. These experiments revealed the organization of the reciprocal mediodorsal-prefrontal connections since wheatgerm agglutinin-horseradish peroxidase is transported effectively in anterograde and retrograde directions. Injections of wheatgerm agglutinin-horseradish peroxidase or fluorescent tracers were placed in different portions of the prefrontal cortex, and the lectin Phaseolus vulgaris leucoagglutinin was injected in the mediodorsal nucleus in order to verify in more detail the point-to-point relationship in the mediodorsal-prefrontal connections. The organization of a number of the subcortical afferents to the mediodorsal nucleus was determined in detail using injections of Phaseolus vulgaris leucoagglutinin, wheatgerm agglutinin-horseradish peroxidase, or tritiated amino acids in areas identified as a source of mediodorsal afferents in the retrograde tracing experiments. These anterograde tracers were injected in different parts of the pallidal complex, the amygdala, the lateral hypothalamus, the lateral entorhinal cortex, the ventral mesencephalon, the superior colliculus and the dorsal tegmental region. The results of the present experiments indicate that the mediodorsal nucleus, on the basis of its cyto-, myelo- and chemoarchitecture as well as the organization of its reciprocal connections with the prefrontal cortex, can be subdivided into a medial, a central, a lateral and a paralamellar segment. Apart from this subdivision along a mediolateral axis, rostrocaudal and dorsoventral differences are also evident in the structural organization and connectivity of the mediodorsal nucleus. A number of subcortical structures send fibres to all parts of the mediodorsal nucleus. The reticular thalamic nucleus projects to the mediodorsal nucleus in a topographical way such that its rostral part is connected with the rostral part of the nucleus, whereas more caudal and ventral areas in the reticular thalamic nucleus are connected with more caudal parts of the mediodorsal nucleus. Regions in the brainstem that project to all parts of the mediodorsal nucleus include the mesencephalic raphé nuclei, the locus coeruleus, the rostral part of the central gray substance and the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Ascending projections to the mammillary nuclei in the rat: a study using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase.

Cells of origin of ascending afferents to the mammillary nuclei and the afferents' fields of termination within these nuclei were studied by using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase in the rat. The pars compacta of the superior central nucleus projects bilaterally to the median region of the medial mammillary nucleus. The ventral tegmental nucleus projects ipsilaterally to the medial mammillary nucleus, except for its median region, in a topographic manner such that the rostrodorsolateral part of the ventral tegmental nucleus projects to the medial quadrant of the medial mammillary nucleus; the rostroventromedial part projects to the dorsal quadrant; the caudodorsolateral part projects to the ventral quadrant; and the caudoventromedial part projects to the lateral quadrant. These projection fields extend throughout the longitudinal axis of the medial mammillary nucleus, except for its most caudal region, to which only the dorsolateral part of the ventral tegmental nucleus projects. This nucleus also projects topographically to the ipsilateral dorsal premammillary nucleus; the rostral part of the ventral tegmental nucleus projects to the dorsal part of the dorsal premammillary nucleus, whereas the caudal part projects to the ventral part. The periaqueductal gray around the dorsal tegmental nucleus projects bilaterally to the supramammillary nucleus. The pars alpha of the pontine periaqueductal gray projects bilaterally to the peripheral part of the lateral mammillary nucleus, whereas the pars ventralis of the dorsal tegmental nucleus projects ipsilaterally to the lateral mammillary nucleus. The results show that the tegmentomammillary projections are organized in a gradient fashion, with the rostral to caudal position of cells of origin within the tegmental nuclei of Gudden being reflected by the medial to lateral position of fields of termination within the mammillary nuclei.

Morphological analysis of the tuberomammillary nucleus in the rat brain: delineation of subgroups with antibody against L-histidine decarboxylase as a marker.

With an antibody specific for L-histidine decarboxylase (HD) in combination with immunohistochemical techniques and retrograde fluorescent tracing, the morphology, distribution, and projections of the histaminergic neurons of the posterior hypothalamus were studied in the adult male rat. Magnocellular neurons, situated on both sides of the mammillary recess and close to the ventral surface of the brain rostral and caudal to the mammillary bodies, were found to contain HD-immunoreactivity (HD-i). In addition to these magnocellular neurons, a substantial number of small and medium-sized neurons were immunostained, as were strands of cells of all sizes bridging the HD-i cell groups. A detailed mapping of the HD-i cells in frontal, sagittal, and horizontal sections showed that these neurons make up one continuous cell group, defined as the tuberomammillary nucleus (TM). This nucleus can be divided into several subgroups. Thus, approximately 600 HD-i neurons situated on each side of the mammillary recess compose the medial subgroup of the TM (TMM). The ventral subgroup of the TM (TMV) consists of some 1,500 neurons situated at the ventral surface of the brain, rostral (TMVr) and caudal (TMVc) to the mammillary bodies. The TMM contains a greater proportion of parvicellular neurons compared to the TMV. About 100 HD-i cells are scattered within the lateral hypothalamic area, the posterior hypothalamic region, the perifornical area, the supramammillary nucleus, and the dorsomedial hypothalamic nucleus. These cells are collectively named the diffuse part of the TM (TMdiff). The morphological differences between the TMM and the TMV did not signal differences in the efferent connections of these subgroups. Thus, single injections of the fluorescent tracer Fast Blue into different regions of the brain, including the spinal cord, resulted in retrograde labeling of HD-i neurons, which were distributed throughout the TM with no discernible topographic pattern. More specifically, each subgroup of the TM contributed projections innervating or passing through a large number of brain regions, including the olfactory bulb, hippocampus, caudate nucleus, paraventricular and supraoptic nuclei of the hypothalamus, cerebellum, tectum, medulla, and spinal cord. The widespread projections of the HD-i neurons contrasted to the more specific projections observed from non HD-i neurons in cell groups situated around the TM. Taken together, these findings suggest that the HD-i cells of the posterior hypothalamus constitute one major nucleus, the TM, and that this nucleus may be subdivided into three components, each of which has diffuse projections throughout the neuraxis.

Histogenesis of the subthalamic nucleus

Literature presents divergent hypotheses on the histogenesis of the subthalamic nucleus. The basal plate of the mesencephalon, the dorsal hypothalamus (or the longitudinal subthalamic zone) and an area closely related to the mammillary nucleus have all been proposed as the site of origin of the neurons of the subthalamic nucleus. However, based on the selective labelling of neurons of this nucleus by the [ 3H]thymidine ARG technique, our results clearly show that a germinative zone lying caudally along the dorsal aspect of the mammillary recess is responsible for the formation of the neurons of the subthalamic nucleus. From this site of origin, the neurons migrate radially and then tangentially and dorsally along the marginal layer of the ventral diencephalon. The present study gives a detailed account of the histogenesis of the subthalamic nucleus of the rat through successive stages of development. Our data also show that the same proliferative neuroepithelial matrix that gives rise to the subthalamic neurons is also responsible for the genesis of the neurons of the supramammillary and submammillothalamic nuclei. Some aspects of the cytological maturation of the neurons of the subthalamic nucleus are also given.

Organization of atriopeptin-like immunoreactive neurons in the central nervous system of the rat.

The atrial natriuretic peptide, atriopeptin, is a circulating hormone that plays an important role in the regulation of fluid and electrolyte homeostasis. Several recent studies have shown that atriopeptin-like immunoreactivity is present within the central nervous system as well as peripheral tissues. In the present report, we describe in detail the organization of atriopeptin-like immunoreactive (APir) perikarya and fibers in the central nervous system of the rat. The most prominent collection of APir perikarya was found in the hypothalamus, adjacent to the anteroventral tip of the third ventricle. Additional groups of APir perikarya were observed along the wall of the third ventricle and in the paraventricular and arcuate nuclei. Separate, smaller groups with distinctive morphology were seen in the lateral hypothalamic area, in the supra-mammillary, medial, and lateral mammillary nuclei, medial habenular nucleus, bed nucleus of the stria terminalis, and the central nucleus of the amygdala. In the pons and brain-stem, APir neurons were observed in the pedunculopontine and laterodorsal tegmental nuclei, as well as in the ventral tegmental area, Barrington's nucleus, the parabrachial nucleus, and the nucleus of the solitary tract. The densest terminal fields of APir fibers were found in the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, the median eminence, and the interpeduncular nucleus. The presence of atriopeptin immunoreactivity within the central nervous system suggests that atriopeptin may function as a central neuromediator. Potential functions of this candidate neuromediator deduced from its anatomical distribution are discussed, including the possibility that atriopeptin may function as both a central neuromediator and a systemic hormone in the regulation of the cardiovascular system.

Ascending projections of the mammillary region in the pigeon: Emphasis on telencephalic connections

The ascending projections of the mammillary region of the hypothalamus and adjacent posterolateral hypothalamus were investigated by autoradiographic and horseradish peroxidase histochemical techniques. Analysis of the anterograde data revealed that the main contingent of mammillary fibers ascends in the medial forebrain bundle (MFB) in the lateral hypothalamic area. These fibers distribute to a number of telencephalic regions via three pathways. (1) Fibers course dorsomedially into the medial and lateral parts of the septum and continue into the hippocampus with a dense terminal field in the parahippocampal area. (2) Laterally coursing fibers project to area corticoidea dorsolateralis, area temporo-parieto-occipitalis, cortex piriformis, and the posterior part of archistriatum. (3) The fibers remaining in the MFB ascend into the "ventral paleostriatum," olfactory tubercle, and into the lateral and ventral borders of the rostral portion of lobus parolfactorius (LPO). Numerous fibers leave the LPO region and course dorsally into the deep layer of the Wulst, hyperstriatum dorsale (HD). Many fibers continue dorsolaterally through the HD and enter an unnamed region of the dorsolateral telencephalon (lateral to the vallecula) at the level of the olfactory bulb. Retrograde transport experiments revealed that the perikarya of origin-of-fiber projections to the parahippocampal area and to the rostral, dorsolateral telencephalon reside not only in nucleus mammillaris lateralis but also in posterolateral hypothalamic cells rostral and dorsal to this nucleus. The projection of these hypothalamic cells to the hippocampal formation and many other telencephalic regions in birds suggests that these cells are similar to the mammalian supramammillary nucleus and posterolateral hypothalamus rather than the mammillary nuclei.

Organization of cerebral cortical afferent systems in the rat. II. Hypothalamocortical projections.

The organization of hypothalamic projections to the cerebral cortex in the rat has been studied using retrograde and anterograde tracer methods. Four separate populations of hypothalamic neurons, which constitute a major source of diffuse cortical innervation, were identified: Tuberal lateral hypothalamic (LHAt) neurons which innervate the cerebral cortex tend to cluster in the perifornical region, in the zona incerta, and along the medial edge of the cerebral peduncle, at levels roughly coextensive with the ventromedial hypothalamic nucleus. Most of these neurons project to the ipsilateral cortex; a small percentage innervate the contralateral cortex, but this varies among cortical terminal fields. The perifornical neurons are organized in a roughly topographic medial-to-lateral relationship with respect to their cortical terminal fields. Field of Forel (FF) neurons, which project primarily to the frontal cortex of the ipsilateral hemisphere, are located just ventral to the medial edge of the medial lemniscus, at the level of the ventromedial basal thalamic nucleus. The more laterally placed neurons innervate the lateral frontal, insular and perirhinal cortex; the more medial neurons, around the mammillothalamic tract, innervate the medial frontopolar, prelimbic, infralimbic, and anterior cingulate cortex. Posterior lateral hypothalamic (LHAp) neurons form a dense cluster spanning the lateral hypothalamus, from the cerebral peduncle to the posterior hypothalamic area at premammillary levels, and extending into the supramammillary nucleus and the adjacent ventral tegmental area. LHAp neurons innervate the entire cerebral cortex, predominantly on the ipsilateral side. Populations of LHAp neurons projecting to different cortical target areas show considerable spatial overlap, but computer plots of the centers of these populations demonstrate a strict topographic relationship with respect to the cerebral cortex. Tuberomammillary (TMN) neurons form a sheet along the ventrolateral surface of the premammillary hypothalamus. About twice as many TMN neurons innervate the ipsilateral, as compared to the contralateral hemisphere; it is not known whether single neurons project to both hemispheres. No topographic organization of the TMN cortical projection is apparent. Injections of different-colored fluorescent dyes into various cortical areas demonstrate that hypothalamic neurons in general have rather restricted cortical terminal fields. Only occasional neurons are found, primarily in LHAt, which are double labeled by injections into different cytoarchitectonic areas.(ABSTRACT TRUNCATED AT 400 WORDS)