Cellular taxonomy and spatial organization of the murine ventral posterior hypothalamus.

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance, and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single-cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell populations in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in selected neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit neuroanatomical parcellation within MB subdivisions and topographic projections to the thalamus. This single-cell transcriptomic atlas of VPH cell types provides a resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits.

Hypothalamic gamma-aminobutyric acid neurons project to the neocortex.

Three groups of gamma-aminobutyric acid--containing neurons were found in the mammillary region of the posterior hypothalamus. The groups correspond to the tuberal, caudal, and postmammillary caudal magnocellular nuclei. Many cells in these nuclei were retrogradely labeled with fast blue after the injection of this fluorescent dye into the neocortex. Immunohistochemical experiments showed that these same neurons also contained the gamma-aminobutyric acid-synthesizing enzyme glutamate decarboxylase. These results provide morphological evidence for a gamma-aminobutyric acid pathway arising in magnocellular neurons of the posterior hypothalamus and innervating the neocortex.

Posterior hypothalamic GABAergic mediation of hippocampal theta in the cat.

The effect of posterior hypothalamic (PH) microinjections of GABAA and GABAB agonists (muscimol and baclophen, respectively) and antagonists (bicuculline and 2-OH saclophen) on spontaneous, sensory and electrically induced hippocampal formation (HPC) theta EEG activity was investigated in freely behaving cats. Administration of GABAergic agonists abolished the theta rhythm recorded from HPC. This effect was reversible. A substantial difference in the recovery time course between frequency versus amplitude and power of hippocampal theta was observed. While theta frequency exhibited a rapid reappearance with a shallow slope, the power and amplitude showed a gradual recovery with a steeper slope. The PH injection of GABAergic antagonists produced HPC theta with increased power. These results demonstrate that both types of GABAergic receptors localized in PH are engaged in mechanisms responsible for generating hippocampal theta oscillations in freely behaving cats. The present study provides additional support for the essential difference between rats and cats in the programming of HPC theta amplitude and frequency. While the PH in rats is involved in programming the frequency of theta rhythm, the same region in cats mainly determines theta amplitude.

Connectivity of an effective hypothalamic surgical target for cluster headache.

The purpose of this study was to look at the connectivity of the posterior inferior hypothalamus in a patient implanted with a deep brain stimulating electrode using probabilistic tractography in conjunction with postoperative MRI scans. In a patient with chronic cluster headache we implanted a deep brain stimulating electrode into the ipsilateral postero-medial hypothalamus to successfully control his pain. To explore the connectivity, we used the surgical target from the postoperative MRI scan as a seed for probabilistic tractography, which was then linked to diffusion weighted imaging data acquired in a group of healthy control subjects. We found highly consistent connections with the reticular nucleus and cerebellum. In some subjects, connections were also seen with the parietal cortices, and the inferior medial frontal gyrus. Our results illustrate important anatomical connections that may explain the functional changes associated with cluster headaches and elucidate possible mechanisms responsible for triggering attacks.

Conditional CRF receptor 1 knockout mice show altered neuronal activation pattern to mild anxiogenic challenge.

RATIONALE: Regional-specific corticotropin-releasing factor receptor 1 (CRF-R1) knockout mice have been generated recently as a tool to dissociate CNS functions modulated by this receptor. In these mice, CRF-R1 function is postnatally inactivated in the anterior forebrain including limbic brain structures but not in the pituitary leading to normal activity of the hypothalamic-pituitary-adrenocortical (HPA) axis under basal conditions and reduced anxiety-related behavior in the light-dark box and the elevated plus maze (EPM) as compared to wild-type (WT) mice (Müller et al., Nat Neurosci 6:1100-1107, 2003). OBJECTIVE: To identify neurobiological correlates underlying this reduced anxiety-like behavior, the expression of c-Fos, an established marker for neuronal activation, which was examined in response to a mild anxiogenic challenge. MATERIALS AND METHODS: Mice were placed for 10 min on the open arm (OA) of the EPM, and regional c-Fos expression was investigated by immunohistochemistry. RESULTS: OA exposure enhanced c-Fos expression in both conditional CRF-R1 knockout and WT mice in a number of brain areas (39 of 55 quantified), including cortical, limbic, thalamic, hypothalamic, and hindbrain regions. The c-Fos response in conditional CRF-R1 knockout animals was reduced in a restricted subset of activated neurons (4 out of 39 regions) located in the medial amygdala, ventral lateral septum, prelimbic cortex, and dorsomedial hypothalamus. CONCLUSIONS: These results underline the importance of limbic CRF-R1 in modulating anxiety-related behavior and suggest that reduced neuronal activation in the identified limbic and hypothalamic key structures of the anxiety circuitry may mediate or contribute to the anxiolytic-like phenotype observed in mice with region-specific deletion of forebrain CRF-R1.

Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat.

No previous report in any species has systematically examined the descending projections of the posterior nucleus of the hypothalamus (PH). The present report describes the descending projections of the PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin. PH fibers mainly descend to the brainstem through two routes: dorsally, within the central tegmental tract, and ventromedially, within the mammillo-tegmental tract and its caudal extension, ventral reticulo-tegmental tracts. PH fibers were found to distribute densely to several nuclei of the brainstem. They are (from rostral to caudal) 1) lateral/ ventrolateral regions of the diencephalo-mesopontine periaqueductal gray (PAG); 2) the peripeduncular nucleus; 3) discrete nuclei of pontomesencephalic central gray (dorsal raphe nucleus, laterodorsal tegmental nucleus, and Barrington's nucleus); 4) the longitudinal extent of the central core of the mesencephalic through meduallary reticular formation (RF); 5) the ventromedial medulla (nucleus gigantocellularis pars alpha, nucleus raphe magnus, and nucleus raphe pallidus); 6) the ventrolateral medulla (nucleus reticularis parvocellularis and the rostral ventrolateral medullary region); and 7) the inferior olivary nucleus. PH fibers originating from the caudal PH distribute much more heavily than those from the rostral PH to the lower brainstem. The PH has been linked to the control of several important functions, including respiration, cardiovascular activity, locomotion, antinociception, and arousal/wakefulness. It is likely that descending PH projections, particularly those to the PAG, the pontomesencephalic RF, Barrington's nucleus, and parts of the ventromedial and ventrolateral medulla, serve a role in a PH modulation of complex behaviors involving integration of respiratory, visceromotor, and somatomotor activity.

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). I. Cytoarchitectonic organization.

The cytoarchitectonic organization of the posterior hypothalamus of the cynomolgus monkey (Macaca fascicularis) was analyzed in Nissl, Golgi, acetylcholinesterase, and reduced silver preparations. The region consists of a number of cell masses that differ considerably in their discreteness and in the homogeneity of their neuronal populations. The nuclei identified include: the medial mamillary nucleus (in which at least three distinct subdivisions can be recognized--a pars medialis, a pars lateralis, and a pars basalis); the small-celled nucleus intercalatus; the large-celled lateral mamillary nucleus; a single premamillary nucleus; the tuberomamillary nucleus; the posterior hypothalamic nucleus; the caudal extension of the lateral hypothalamic area; the supramamillary area; and the paramamillary nucleus (which appears to correspond to the nucleus of the ansa lenticularis of other workers). As a basis for the subsequent experimental study of the efferent connections of the posterior hypothalamus, the location of each of these cell masses is described and illustrated in a series of low-power photomicrographs, as are the form and distribution of the resident neuronal populations of the various components of the mamillary complex as seen in Golgi preparations.

Telencephalic projections in two teleost species.

The efferent pathways of the telencephalon were investigated in the percomorph Eugerres and the berycomorph Holocentrus. One telencephalic hemisphere was resected by suction and the animals were perfused 7-35 days thereafter. The brains were processed according to a modification (Method 7 in Ebbesson, '70) of the Fink-Heimer ('67) technique for selective silver impregnation of degenerating axons and terminals. Some fibers emerging from the lesioned telencephalic hemisphere terminate upon the contralateral hemisphere. The large bulk of efferent fibers, however, descends into the ipsilateral diencephalon and gives off the so-called strio-tectal bundle (STB) as well as the medial forebrain bundle (MFB). The remaining contingent eventually splits into the so-called strio-lobar bundle (SLB) and the lateral forebrain (LFB), but, previous to splitting, it contributes most of the telencephalic projection to the optic tectum in Eugerres, and gives abundant terminals to the ipsilateral nucleus rotundus or prethalamicus in both Eugerres and Holocentrus. The STB conveys all telencephalo-tectal fibers in Holocentrus, and some of them in Eugerres. Telencephalic efferents teminate ipsilaterally in the middle level of the tectum's stratum griseum centrale; in Holocentrus there is also a small projection to the stratum opticum. The MFB terminates at the caudal hypothalamus and gives terminals all along its course. The LFB also gives terminals all along its course and terminates upon a nucleus located between the midline and the corpus glomerulosum. The SLB spreads out and terminates in the inferior lobe of the hypothalamus.

A cytoarchitectonic atlas of the mouse hypothalamus.

A description of the organization, areas, and cell groups within the hypothalamus of the mouse is presented in detail. Photomicrographs of cell-stained serial sections through the hypothalamus in frontal, sagittal and horizontal planes are included. The hypothalamus has been divided basically into medial and lateral parts with most well-defined cell groups or nuclei lying within the medial subdivision and surrounded by diffuse collections of cells referred to as areas. The heterogenetiy of cell types within most hypothalamic nuclei and areas has been emphasized with the consequent implications for heterogeneity of neuronal connections and of functions. Recently introduced neuroanatomical techniques permitting increased attention to the cellular level of organization have demonstrated precise connections and functional localization of cells within the hypothalamus. While cytoarchitectonic distinctions imply functional distinctions, morphological and experimental evidence suggest the existence also of systems of cells which transcend conventional cytoarchitectonic boundaries, the cells within each system being interconnected functionally or neuronally.

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). II. Efferent connections.

The efferent connections of the posterior hypothalamus have been analyzed autoradiographically in a series of eight cynomolgus monkey (Macaca fascicularis) brains with injections of 3H-amino acids in different regions of the mamillary complex and the surrounding areas. The medial mamillary nucleus was found to project through the mamillothalamic tract to the ipsilateral anteroventral, anteromedial, and interanteromedial nuclei, and by way of the mamillotegmental tract principally to the deep tegmental nucleus (of Gudden). It also appears to contribute fibers to the medial forebrain bundle, some of which reach as far rostrally as the medial septal nucleus. The lateral mamillary nucleus projects through the mamillothalamic tract bilaterally upon the anterodorsal nuclei of the thalamus, and through the mamillotegmental system to the dorsal tegmental nucleus; it also appears to contribute fibers to the medial forebrain bundle. The supramamillary area has extensive ascending and descending connections that are distributed with the medial forebrain bundle to the hypothalamus and rostral midbrain; in addition, it gives rise to an unusually well-defined projection to field CA2 of the hippocampus and to a narrow zone overlying the outer part of the granule cell layer and the adjoining part of the molecular layer of the dentate gyrus. We have not been able to distinguish the connections of the posterior hypothalamic nucleus from those of the caudal part of the lateral hypothalamic area: they both appear to contribute substantially to the ascending components of the medial forebrain bundle, and through its descending projection to the tegmental fields of the midbrain, the nucleus centralis superior of the raphe complex, the locus coeruleus, and the central gray as far caudally as the facial nerve. Their further projections to the spinal cord were not examined. Viewed broadly, and in the light of previous work, our observations confirm, once again, the constancy of the connections of the hypothalamus in the mammalian brain, and the pivotal position that the posterior hypothalamus occupies in the elaborate system of connections that links the limbic areas of the forebrain with the complex of structures that Nauta has aptly designated the "midbrain limbic region."

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.

An HRP study of the connections of the subfornical organ of the rat.

The connections of the subfornical organ (SFO) were investigated by using the HRP technique. Injections into the SFO labeled neurons in the medial septum, but not in lateral septum nor in the diagonal band nucleus. Labeled cells were observed in the median preoptic nucleus, below the ependyma of the third ventricle, in the dorsal preoptic region near the anterior commissure, and diffusely throughout the medial preoptic and anterior hypothalamic areas. Fibers were followed from the ventral stalk of the SFO. Precommissural fibers enter the median preoptic nucleus where many of them appear to terminate. Others continue on to the medial septum, the OVLT, the supraoptic nucleus, and suprachiasmatic nucleus. HRP injections into the median preoptic nucleus labeled many neurons in the SFO. Postcommissural fibers reach the hypothalamus by descending along the walls of the ventricle in the subependymal space, by traveling in the columns of the fornix and the medial corticohypothalamic tract, or by passing through the paraventricular nucleus of the thalamus. Some postcommissural fibers turn rostrally and enter the median preoptic nucleus while others join precommissural fibers bound for the supraoptic nucleus. More caudally directed fibers appear to innervate the paraventricular nucleus of the hypothalamus and the medial preoptic and anterior hypothalamic areas. HRP injections into the paraventricular nucleus of the hypothalamus labeled neurons in the SFO. These findings corroborate and extend previous work in describing neural connections between two brain regions that are important for fluid balance.

Localization of forebrain neurons which project directly to the medulla and spinal cord of the rat by retrograde tracing with wheat germ agglutinin.

Wheat germ agglutinin (WGA) in a slow-release polyacrylamide gel pellet was implanted in the medulla or spinal cord of the rat. Large numbers of retrogradely labeled cells were visualized by immunocytochemical procedures in specific nuclei of the forebrain mainly ipsilateral to the implant site following implants as far caudal as the sacral segments of the spinal cord. Total average number of labeled forebrain cells (three brains per category; 100 micron per 150 micron of brain tissue were examined microscopically): medulla, 2,115; cervical, 1,878; lumbar, 1,017; sacral, 385. After WGA-gel implants in the medulla or cervical cord the majority of retrogradely labeled neurons were seen in the lateral hypothalamic area, the zona incerta, and in subdivisions of the paraventricular nucleus. A continuum of labeled cells extended from the caudal part of the paraventricular nucleus into the posterior hypothalamus and into the central gray of the midbrain. Labeled cells were also seen in the medial basal hypothalamus and the rostral part of the bed nucleus of the stria terminalis. A few labeled cells were observed in the medial and lateral preoptic areas, the rostral part of the paraventricular nucleus, and in the arcuate nucleus. Following WGA-gel implants in the lumbar or sacral cord many retrogradely labeled cells were observed mainly in the paraventricular nucleus, the lateral hypothalamus, zona incerta, medial basal hypothalamus, and posterior hypothalamic area. The continuum of labeled cells described above was also seen following these implants. Our data indicate that the lateral hypothalamus and zona incerta, as well as specific parts of the paraventricular nucleus, are major loci of neurons which project directly to the medulla and spinal cord of the rat. The consistency with which labeled cells were localized across all brains examined within categories of implant sites and the large numbers of labeled cells counted within these areas appeared to verify the sensitivity of our retrograde tracing method. Therefore, we interpret the paucity or absence of labeled cells in particular brain regions to indicate that cells of these regions do not project to the medulla or spinal cord.

The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat.

Direct projections from the forebrain to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus in the rat medulla were mapped in detail using both retrograde axonal transport of the fluorescent tracer True Blue and anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). In the retrograde tracing studies, cell groups in the medial prefrontal cortex, lateral prefrontal cortex (primarily ventral and posterior agranular insular cortex), bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular, arcuate, and posterolateral areas of the hypothalamus were shown to project to the NTS and in some cases also to the dorsal motor nucleus of the vagus. The prefrontal cortical areas projecting to the NTS apparently overlap to a large degree with those cortical areas receiving mediodorsal thalamic and dopaminergic input. The retrogradely labeled cortical cells were situated in deep layers of the rat prefrontal cortex. The anterograde tracing studies revealed a prominent topography in the mediolateral termination pattern of forebrain projections to the rostral part of the NTS and to the dorsal pons. The projections to the NTS were generally bilateral, except for projections from the central nucleus of the amygdala and bed nucleus of the stria terminalis which were predominantly ipsilateral. The prefrontal cortical projections to the NTS travel through the cerebral peduncle and pyramidal tract and terminate throughout the rostrocaudal extent of the NTS. Specifically, the prefrontal cortex innervates dorsal portions of the NTS (lateral part of the dorsal division of the medial solitary nucleus, dorsal part of the lateral solitary nucleus and the caudal midline region of the commissural nucleus), areas which receive relatively sparse subcortical projections. These dorsal portions of the NTS receive major primary afferent projections from the vagal and glossopharyngeal nerves. In contrast, the subcortical projections, which travel through the midbrain and pontine tegmentum, terminate most heavily in the ventral portions of the NTS, i.e., the area immediately dorsal and lateral to the dorsal motor nucleus of the vagus. Only the paraventricular hypothalamic nucleus has substantial terminals throughout the dorsal motor nucleus of the vagus. Hypothalamic cell groups innervate the area postrema and, along with the prefrontal cortex, innervate the zone subjacent to the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypothalamic inferior lobe and lateral torus connections in a percomorph teleost, the red cichlid (Hemichromis lifalili).

The neuroanatomic connections of the inferior lobe and the lateral torus of the percomorph Hemichromis lifalili were investigated by 1,1', dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate (DiI) tracing. The inferior lobe and the lateral torus both receive afferents from the secondary gustatory nucleus. Additional afferents reach the inferior lobe from the nucleus glomerulosus, nucleus suprachiasmaticus, dorsal and central posterior thalamic nucleus, nucleus lateralis valvulae, magnocellular part of the magnocellular nucleus of the preoptic region, caudal nucleus of the preglomerular region, posterior tuberal nucleus, area dorsalis of the telencephalon, and a tegmental nucleus (T2). Efferents from the inferior lobe and the lateral torus terminate in the dorsal hypothalamic neuropil and corpus mamillare. Furthermore, the inferior lobe projects to the medial nucleus of the lateral tuberal hypothalamus and perhaps makes axo-axonal synapses in the tractus tectobulbaris rectus. The inferior lobe and the torus lateralis have reciprocal connections with the preglomerular tertiary gustatory nucleus and posterior thalamic nucleus and are also mutually interconnected. The inferior lobe is also reciprocally connected with the medial nucleus of the preglomerular region, reticular formation and sparsely with the anterior dorsal thalamic and the ventromedial thalamic nuclei. Thus, whereas the lateral torus is exclusively connected with the gustatory system, the inferior lobe is of a multisensory nature. In comparison with the goldfish (Carassius auratus), the connectivity pattern of the inferior lobe of Hemichromis lifalili reflects its specialization with respect to the visual system, as it receives qualitative (i.e., dorsal posterior, anterior, and ventromedial thalamic nuclei) as well as quantitative (i.e., nucleus glomerulosus) additional visual input.

Antagonism of central pressor response to angiotensin II by alpha-human atrial natriuretic polypeptide at the preoptic area and posterior hypothalamus in rats.

Effects of alpha-human atrial natriuretic polypeptides (alpha-hANP) on pressor responses to angiotensin II (AII) were assessed at the preoptic area, posterior hypothalamus and central amygdaloid nucleus (ACE) in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats. Angiotensin II, administered intracerebroventricularly, at a dose of 100 ng produced a marked pressor response in hypertensive, as well as in normotensive rats and the response was potentiated in hypertensive rats. The response was antagonized in a dose-dependent manner by administration of alpha-hANP into the preoptic area and posterior hypothalamus but not to the amygdaloid nucleus. The antagonism was more marked in hypertensive than in normotensive rats. Angiotensin II, when injected directly to the preoptic area at a small dose of 10 ng similarly evoked a marked pressor response, which was augmented in hypertensive rats. This response was also antagonized by coadministration of alpha-hANP to the preoptic area in hypertensive but not in normotensive rats. The results suggest that the antagonistic relationship between ANP and AII exists at the preoptic area and posterior hypothalamus, probably implying that the activity of the ANP and AII systems in brain play a role in centrally controlling the cardiovascular system and is altered at these areas in genetically hypertensive rats.

The distribution of histaminergic axons in the superior colliculus of the cat.

The histaminergic projection from the hypothalamus to the superior colliculus was examined immunohistochemically in the cat brain using an antibody to histamine. The source of histaminergic fibers in the brain is a group of neurons in the posterior hypothalamus, located primarily in ventrolateral and periventricular regions and collectively referred to as the tuberomammillary nucleus. All laminae of the superior colliculus--including the superficial, intermediate, and deep layers, as well as the central gray--were blanketed with histamine-immunoreactive axonal fibers. Overall, labeling in the superior colliculus was moderately dense compared to other locations in the cat brain, with some variation in fiber density. Individual labeled fibers resembled histaminergic fibers described previously in the brain. Labeled axonal fibers showed infrequent branching and were beaded with numerous en passant varicosities that were typically 1 micron or smaller, but as large as 2.5 micron in diameter. Varicosity size differed significantly at different depths in the colliculus. The histaminergic projection appears to be separate from a previously reported, apparently non-histaminergic projection from neurons in the dorsal hypothalamic area to discrete regions of intermediate and deep colliculus. These results indicate that the histaminergic projection from the tuberomammillary nucleus of the hypothalamus projects extensively throughout the superior colliculus. Histamine, which is believed to act as a neuromodulator in the brain, is in a position to influence sensory and motor-related processes in every layer of the cat superior colliculus.

Stimulation of H fields of Forel decreases total lung resistance in dogs.

Although there is considerable evidence that the H fields of Forel of the posterior diencephalon play an important role in the regulation of cardiovascular function, little is known about the role these areas play in the control of airway caliber. In chloralose-anesthetized paralyzed dogs, we used both electrical and chemical means to stimulate the H fields of Forel, while we monitored breath-by-breath changes in total lung resistance (TLR), a functional index of airway caliber. Electrical stimulation (200-250 microA, 80 Hz, 0.75 ms) of 82 histologically confirmed sites significantly decreased TLR from 9.2 +/- 0.4 to 7.9 +/- 0.4 cmH2O.l-1.s (P less than 0.01). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade with propranolol but was abolished by cholinergic blockade with atropine. The increases in airway caliber evoked by stimulation were often accompanied by increases in phrenic nerve activity. Chemical stimulation of 21 of 82 sites with microinjections of DL-homocysteic acid (83 nl, 0.2 and 0.5 M), which stimulates cell bodies but not fibers of passage, also decreased TLR from 8.3 +/- 0.5 to 7.3 +/- 0.5 cmH2O.l-1.s (P less than 0.03). We conclude that stimulation of cell bodies in the H fields of Forel produces bronchodilation by withdrawal of cholinergic tone to airway smooth muscle.

Central dopaminergic neurons in tilapia: effects of gonadectomy and hypothalamic lesion.

The effects of gonadectomy, testosterone and estrogen on the dopamine (DA) neurons were examined by measuring the concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the brain and pituitary of male tilapia. The tuberal area and the pituitary had significantly high levels of DA and low levels of DOPAC, indicating the existence of a rich dopaminergic innervation in these areas. Gonadectomy and sex steroid replacement had no effect on DA and DOPAC levels. Preoptic lesions (14 days survival period) significantly increased DA levels of the pituitary, indicating a possible existence of a preoptico-hypophysial neural system that inhibits pituitary DA synthesis in tilapia. The lack of effect by preoptic (4 days survival period) and posterior hypothalamic lesions on the DA content of the pituitary indicates the absence of dopaminergic innervation of the pituitary by the preoptic and the posterior hypothalamus. Instead, the overall results do suggest the anterior periventricular area as a possible source of pituitary dopaminergic innervation.

The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation.

A two-lever choice paradigm with concurrent variable interval schedules of reward was used to measure the growth in the subjective magnitude of reward as a function of current, by finding the adjustment in the stimulating current required to offset a given difference in the rates at which two rewards were received. Increasing current by a factor of 2 increased subjective reward magnitude by a factor ranging from as little as 3 to as much as 4,000. This range was about as great between electrodes within one rat as between electrodes and rats. In the light of earlier findings regarding the equivalent effects of increments is current and pulse frequency, these large differences cannot readily be explained by differing fiber densities at the site of stimulation. It is suggested that the medial forebrain bundle terminates in more than one spatio-temporal integration mechanism. The magnitude of the spatio-temporally integrated effect of a barrage of action potentials in the reward-relevant axons depends on which subset of reward-relevant axons is excited by the stimulation.