Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow.

Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifier of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.

Role of 5-HT(1A) receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation.

The dorsomedial hypothalamus (DMH) is an essential brain region for the integration of the physiological response to psychological stressors. The cardiovascular components of the response include increases in blood pressure, heart rate and the activity of sympathetic nerves to the kidney, skin, brown adipose tissue, and heart. Neurons in the rostral ventrolateral medulla (RVLM) and in the region of the medullary raphe are important components of the descending pathways that mediate the cardiovascular response to the DMH activation. Activation of 5-hydroxytryptamine 1A (5-HT(1A)) receptors in the brain leads to a suppression of the cardiac and sympathetic vasomotor components of the DMH-evoked response and of the response to acute psychological stress. In this study we showed that intracisternal injection of a low dose (1 microg/kg) of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), significantly reduced the increases in heart rate and renal sympathetic nerve activity evoked by disinhibition of the DMH, but had no effect on these responses when injected intravenously. Subsequent intracisternal administration of the 5-HT(1A) receptor antagonist WAY-100635 restored the DMH-evoked cardiovascular responses to levels observed before 8-OH-DPAT administration. Bilateral microinjections of 8-OH-DPAT (200 pmol on each side) into the RVLM, however, did not significantly affect the cardiovascular response to disinhibition of the DMH. These observations demonstrate that activation of 5-HT(1A) receptors within the lower brainstem, but not in the RVLM, can powerfully suppress the cardiovascular response evoked from the DMH.

Differential expression of hypothalamic CART mRNA in response to body weight change following different dietary interventions.

Cocaine- and amphetamine-regulated transcript (CART) peptide is widely expressed in the hypothalamus and is involved in the central regulation of energy balance. Using in situ hybridization, this study examined the roles of CART peptide in the hypothalamus of diet-induced obese (DIO) or diet-resistant (DR) mice under different dietary interventions including high-fat (HF), low-fat (LF) and pair-feeding (PF) diet for 6 weeks. Pair feeding the energy intake of the DIO and DR mice was used to determine whether there is an inherent difference in baseline CART expression that may cause the DIO and DR phenotypes. The results demonstrated that CART mRNA expression in the hypothalamus of the DIO mice responded differently on the high-fat diet compared to DR mice. The arcuate nucleus and paraventricular nucleus showed a significant reduction in CART mRNA expression in DIO mice compared to DR mice on the HF diet (-19.6%, p=0.019; -26.1%, p=0.003); whilst a profound increase in CART mRNA expression was observed in the dorsomedial nucleus and lateral hypothalamic area (+44.5%, p=0.007; +37.4%, p=0.033). Our study suggests that the decrease of CART mRNA expression in Arc and PVN regions of DIO mice may contribute to the development of high-fat diet-induced obesity. In addition, CART in the dorsomedial nucleus (DM) of hypothalamus and lateral hypothalamus (LH) may be involved in the activation of an orexigenic effect. Since pair feeding of the high-fat diet eliminated both the body weight and CART mRNA differences between the DIO and DR mice, it is likely that their alterations in gene expression were a consequence of their dissimilar body weight levels.

The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms.

Circadian rhythms of behavior and physiology can be entrained by daily cycles of restricted food availability, but the pathways that mediate food entrainment are unknown. The dorsomedial hypothalamic nucleus (DMH) is critical for the expression of circadian rhythms and receives input from systems that monitor food availability. Here we report that restricted feeding synchronized the daily rhythm of DMH activity in rats such that c-Fos expression in the DMH was highest at scheduled mealtime. During food restriction, unlesioned rats showed a marked preprandial rise in locomotor activity, body temperature and wakefulness, and these responses were blocked by cell-specific lesions in the DMH. Furthermore, the degree of food entrainment correlated with the number of remaining DMH neurons, and lesions in cell groups surrounding the DMH did not block entrainment by food. These results establish that the neurons of the DMH have a critical role in the expression of food-entrainable circadian rhythms.

Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state.

The circadian clock housed in the suprachiasmatic nucleus (SCN) controls various circadian rhythms including daily sleep-wake cycles. Using dual tract-tracing, we recently showed that the medial preoptic area (MPA), subparaventricular zone (SPVZ) and dorsomedial hypothalamic nucleus (DMH) are well positioned to relay SCN output to two key sleep-promoting nuclei, namely, the ventrolateral and median preoptic nuclei. The present study examined the possibility that these three nuclei may link the SCN with wake-regulatory neuronal groups. Biotinylated dextran-amine with or without cholera toxin B subunit was injected into selected main targets of SCN efferents; the retrograde labeling in the SCN was previously analyzed. Here, anterograde labeling was analyzed in immunohistochemically identified cholinergic, orexin/hypocretin-containing and aminergic cell groups. Tracer injections into the MPA, SPVZ and DMH resulted in moderate to dense anterograde labeling of varicose fibers in the orexin field and the tuberomammillary nucleus. The locus coeruleus, particularly the dendritic field, contained moderate anterograde labeling from the MPA and DMH. The ventral tegmental area, dorsal raphe nucleus, and laterodorsal tegmental nucleus all showed moderate anterograde labeling from the DMH. The substantia innominata showed moderate anterograde labeling from the MPA. These results suggest that the MPA, SPVZ and DMH are possible relay nuclei for indirect SCN projections not only to sleep-promoting preoptic nuclei as previously shown, but also to wake-regulatory cell groups throughout the brain. In the absence of major direct SCN projections to most of these sleep/wake-regulatory regions, indirect neuronal pathways probably play an important role in the circadian control of sleep-wake cycles and other physiological functions.

Medial prefrontal cortical integration of psychological stress in rats.

The present study aimed to determine whether the medial prefrontal cortex (mPFC) (prelimbic and infralimbic regions) is implicated in the integration of a stress response. Sprague-Dawely rats were implanted with telemetry probes and guide cannulae so that either muscimol or vehicle could be administered locally within the mPFC or dorsomedial hypothalamus (DMH). The heart rate and blood pressure of rats was continuously recorded as either muscimol or vehicle was administered centrally and rats were either exposed to restraint stress or left alone in their home cages. After the stress challenge, or equivalent period, rats that had received intra-mPFC injections were processed for immunohistochemical detection of Fos throughout the neuraxis. Bilateral microinjection of muscimol into the mPFC had no effect upon either baseline cardiovascular parameters or restraint stress-induced tachycardia or pressor responses whereas, in the DMH, pretreatment with muscimol attenuated the cardiovascular stress response. Analysis of Fos expression throughout the CNS of nonstressed rats showed no effect of muscimol injections into the mPFC on baseline expression in the nuclei examined. In contrast, rats that had received muscimol injections into their mPFC and were subsequently restrained exhibited an increase in the number of Fos-positive cells in the DMH, medial amygdala, and medial nucleus tractus solitarius as compared to vehicle-injected rats that experienced restraint stress. These results indicate that, during acute psychological stress, the mPFC does not modulate the cardiovascular system in rats but does inhibit specific subcortical nuclei to exert control over aspects of an integrated response to a stressor.

Organisation of the human dorsomedial hypothalamic nucleus.

This study used acetylcholinesterase (AChE) histochemistry to reveal the organization of the dorsomedial hypothalamic nucleus (DM) in the human. Topographically, the human DM is similar to DM in the monkey and rat. It is wedged between the paraventricular nucleus, dorsally, and the ventromedial nucleus, ventrally. Laterally, DM borders the lateral hypothalamic area while medially it approaches the 3rd ventricle. The AChE staining distinguished two subcompartments of the human DM: the larger diffuse and the smaller compact DM. The subcompartmental organization of the human DM appears homologous to that found in the monkey and less complex than that reported in rats. Understanding of the organization of DM creates meaningful anatomical reference for physiological and pharmacological studies in the human hypothalamus.

The influence of dorsomedial hypothalamic nucleus on contralateral paraventricular nucleus in NMDA-mediated cardiovascular responses.

Dorsomedial (DMH) and paraventricular nuclei (PVN) are two important hypothalamic structures involved in the central regulation of cardiovascular regulation. L-Glutamic acid and gamma-aminobutyric acid (GABA) were demonstrated to elicit cardiovascular responses when administered via intracerebroventricular injection or parenchymal microinjections into the hypothalamic nuclei, participating in central cardiovascular regulation. In this study the interaction between the DMH and the PVN were investigated by means of microinjection and microdialysis techniques in Sprague-Dawley rats. Stereotaxic surgery was performed for the insertion of intracerebral parenchymal microinjection cannula into the right DMH and microdialysis probe into the left PVN. After a recovery period of 3 days, the iliac artery was cannulated for monitoring pulsatile blood pressure and heart rate by means of pressure transducer connected to a polygraph. Microinjection of 50 pmol NMDA into the DMH was performed and microdialysis perfusates were collected simultaneously from the PVN in the conscious rat model. L-Glutamic acid and GABA levels were analyzed by an isocratic HPLC method with the aid of a fluorescent detector. Microinjection of 50 pmol NMDA into the DMH produced significant increases in mean arterial pressure and heart rate. NMDA microinjection into the DMH produced a significant increase in L-glutamic acid release in the PVN, but no significant change in GABA release was observed. These results may indicate that stimulation of the DMH by NMDA results in subsequent stimulation of the PVN.

Anatomical and functional evidence for a stress-responsive, monoamine-accumulating area in the dorsomedial hypothalamus of adult rat brain.

The dorsomedial hypothalamus (DMH) plays an important role in relaying information to neural pathways mediating neuroendocrine, autonomic, and behavioral responses to stress. Evidence suggests that the DMH is a structurally and functionally diverse integrative structure that contributes to both facilitation and inhibition of the hypothalamo-pituitary-adrenal axis, depending on the nature of the stimulus and the specific neural circuits involved. Previous studies have determined that stress or stress-related stimuli elevate tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine, and noradrenaline selectively within the DMH. In order to determine the specific region of the rat DMH involved, we used high-performance liquid chromatography with electrochemical detection to measure tissue concentrations of 5-HT, 5-HIAA, dopamine, and noradrenaline within five different subregions of the DMH in adult female Lewis and Fischer rats immediately or 4 h following a 30-min period of restraint stress. Compared to unrestrained control rats, restrained rats had elevated concentrations of 5-HT, 5-HIAA, dopamine, and noradrenaline immediately after a 30-min period of restraint and had elevated concentrations of 5-HT 4 h following the onset of a 30-min period of restraint stress. These effects were confined to a specific region that included medial portions of the dorsal hypothalamic area and dorsal ependymal, subependymal, and neuronal components of the periventricular nucleus. Furthermore, these effects were observed in Lewis rats, but not Fischer rats, two closely related rat strains with well-documented differences in neurochemical, neuroendocrine, autonomic, and behavioral responses to stress. These data provide support for the existence of a stress-responsive, amine-accumulating area in the DMH that may play an important role in the differential stress responsiveness of Lewis and Fischer rats.

Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.

Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function.

The dorsomedial hypothalamic nucleus revisited: 1998 update.

This article reviews data that have accumulated since the early 1970s on the role of the dorsomedial hypothalamic nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial hypothalamic nucleus (VMN) and the lateral hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.

Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHAL in the rat.

Possible inputs to the DMH were studied first using the fluorescent retrograde tracer Fluorogold, and identified cell groups were then injected with the anterograde tracer PHAL to examine the distribution of labeled axons in and around the DMH. From this work, we conclude that the majority of inputs to the DMH arise in the hypothalamus, although there are a few significant projections from the telencephalon and brainstem. With few exceptions, each major nucleus and area of the hypothalamus provides inputs to the DMH. Telencephalic inputs arise mainly in the ventral subiculum, infralimbic area of the prefrontal cortex, lateral septal nucleus, and bed nuclei of the stria terminalis. The majority of brainstem inputs arise in the periaqueductal gray, parabrachial nucleus, and ventrolateral medulla. In addition, it now seems clear that inputs to the DMH use only a few discrete pathways. Descending inputs course through a periventricular pathway through the hypothalamic periventricular zone, a medial pathway that follows the medial corticohypothalamic tract, and a lateral pathway traveling through medial parts of the medial forebrain bundle. Ascending inputs arrive through a midbrain periventricular pathway that travels adjacent to the cerebral aqueduct in the periaqueductal gray, and through a brainstem lateral pathway that travels through central and ventral midbrain tegmental fields and enters the hypothalamus, and then the DMH from more lateral parts of the medial forebrain bundle. The results are discussed in relation to evidence for involvement of the DMH in ingestive behavior, and diurnal and stress-induced corticosterone secretion.

Contribution of the ascending cholinergic pathways in the production of ultrasonic vocalization in the rat.

It has been well documented that cholinergic stimulation of the mediobasal forebrain structures induces 20-30 kHz ultrasonic vocalization in adult rats. If the cholinergic system plays a triggering role for ultrasonic vocalization, the question arises as to where the source of the cholinergic fibres, which innervate the mediobasal forebrain and induce vocalization, is located. In the present study, the role of the ascending cholinergic projection from the ponto-mesencephalic cholinergic nuclei to the mediobasal hypothalamic-preoptic region in production of 22 kHz calls was investigated. Cholinergic neurons were stimulated by local injection of L-glutamate and eventual vocalization was recorded by a S200 bat detector and analyzed sonographically. Intracerebral injection of L-glutamate into the laterodorsal tegmental nucleus induced short latency, 20-30 kHz ultrasonic calls. Sound frequency (pitch) and single call duration of the L-glutamate-induced vocalization did not differ from those obtained by cholinergic stimulation of the mediobasal hypothalamic-preoptic region with carbachol. However, L-glutamate stimulation of the laterodorsal tegmental nucleus was ineffective or less effective in 70% of responses, when the terminal fields in the mediobasal hypothalamic-preoptic region were pretreated with scopolamine, a muscarinic antagonist. The results demonstrate that the ascending cholinergic projection from the laterodorsal tegmental nucleus plays a triggering role for 20-20 kHz vocalization in adult rats.

Increased plasma IGF-1 levels but lack of changes in adipocyte glucose transport in weanling rats with dorsomedial hypothalamic nucleus lesions 1 year after lesion production.

Experimental destruction of the dorsomedial hypothalamic nuclei (DMN) in weanling rats exerts an antiaging effect by preventing microalbuminuria and kidney lesions both 1 month and 1 year after lesion production. In the present study we report further on antiaging effects of DMN lesions (DMNL) by measuring glucose transport into adipocytes and plasma levels of insulin-like growth factors 1 and 2 (IGF-I, IGF-II). Male and female weanling Sprague-Dawley rats received bilateral electrolytic lesions in the DMN; sham-operated animals served as controls (SCON). The rats were maintained for 1 year and food intake was measured 3 weeks after surgery and 3 weeks prior to sacrifice. As expected, DMNL resulted in profound reductions of body weight and food intake, with male DMNL rats showing higher body weights and body weight gains than their female counterparts. The same was true of the respective SCON. In male DMNL rats, carcass fat in absolute terms was significantly reduced vs. SCON, but it was comparable among all groups when expressed in percent. Lean body mass (LBM), although significantly reduced in absolute terms in DMNL rats vs. SCON, was, however, significantly higher in male DMNL vs. SCON when expressed in percent, but not in females. LBM laid down per food energy taken in was higher in DMNL rats of both sexes than in their respective SCON. Efficiency of food utilization was normal in male DMNL vs. male SCON but was higher in female DMNL vs. SCON. Both male and female DMNL rats had significantly higher plasma IGF-1 concentrations than their respective SCON, and male DMNL rats had higher values than female DMNL rats. Plasma concentrations of IGF-II were significantly higher in DMNL vs. SCON, but only in females. Under both basal and insulin-stimulated conditions, DMNL rats had normal 3-0-methylglucose flux in adipocytes from epididymal fat pads vs. SCON. However, DMNL and SCON responded similarly to the stimulating effect of insulin. Although one-year-old rats may not be considered "aged", we do consider the observed lack of a drop in plasma IGF-I levels that occurs with aging as an "anti-aging" effect of DMN lesions.

Afferent projections to the lateral and dorsomedial hypothalamus in a lizard, Gekko gecko.

Afferent projections to the lateral hypothalamic area and dorsomedial hypothalamic nucleus of the lizard Gekko gecko were studied after applications of wheat germ agglutinin conjugated to horseradish peroxidase. Large applications into the hypothalamus labeled several telencephalic populations not observed after smaller injections. These included the rostrolateral area of the dorsal cortex, a sheet of cells deep to the caudal pole of the lateral cortex, the external amygdala, and part of the dorsal ventricular ridge. Other populations were labeled in the diencephalon, including the supraoptic nucleus and nucleus ovalis; in the medulla the medial reticular area was labeled. Injections into the lateral hypothalamic area labeled neurons in the rostrolateral dorsal cortex, anterior, lateral, and dorsal septal nuclei, the striatoamygdalar area, nucleus accumbens, vertical limb of the diagonal band, nucleus of the accessory olfactory tract, the interstitial, ventral anterior, and ventral posterior amygdalar nuclei, several hypothalamic nuclei, and the posteroventral thalamic nucleus. Labeled brainstem populations included the ventral tegmental area, torus semicircularis, parvocellular and ventral isthmal nuclei, superior raphe, and the solitary nucleus. Injections in the dorsomedial hypothalamic nucleus labeled neurons in the rostral and caudolateral poles of the dorsal cortex, anterior septal nucleus, horizontal limb of the diagonal band, nucleus of the anterior commissure, several hypothalamic areas, the lateral habenula, the posteroventral thalamic nucleus, and cells scattered around the dorsolateral anterior thalamic nuclei. Labeled brainstem populations included the torus semicircularis, ventral tegmental area, superior raphe, parvocellular and ventral isthmal nuclei, and the lateral dorsal tegmental nucleus. The results of these studies are compared with findings in amphibians and mammals.

Alterations in behavioral responses to stressors following excitotoxin lesions of dorsomedial hypothalamic regions.

The dorsomedial hypothalamus is important for regulation of cardiovascular responses associated with emotional arousal. This region has also been identified as a component of neural circuitry involved in fear/anxiety, yet clear evidence as to the effects of lesioning on stress-related behaviors is missing. In this study, we lesioned the dorsomedial hypothalamic region with the neurotoxin, ibotenic acid (IBO; 2.0 micrograms in 0.2 microliter), and studied the impact on spontaneous and unlearned behavioral responses to stressors. In the open field test, we observed non-generalized increases in motility parameters in the IBO rats with the differences occurring in the latter two-thirds of the test. In the elevated plus-maze, the IBO rats displayed a classic anxiolytic response with a greater proportion of entries into (and greater time spent in) the open arms of the maze. In the environment-specific social interaction (SI) test, the IBO rats showed a normal familiar/unfamiliar environment discrimination with respect to Total SI; however, the composition of the behaviors ('curiosity' vs. physical contact) by the IBO rats was markedly altered, with there being a 2-fold increase in non-violent physical interactions. Additionally, the differences in these traditional indices of anxiety were associated with lesioned animals exhibiting greater acoustic startle responsiveness than controls as a function of prepulse intensity. Overall, the results following IBO lesions indicate an altered responsiveness to sudden stressors, particularly as relates to novelty or exploration-oriented behaviors. The hypothalamic lesion may, therefore, have resulted in a disinhibition of normally suppressed responding to innate fear or challenging stimuli. This study contributes to those that have begun to define neural interactions that are essential for integrated stress responses.

[Biological characteristics of neurons of dorsal vagal nucleus]. / Biologicheskie osobennosti neironov dorsalnogo iadra vagusa.

Stereological, histochemical, and electron microscopic approaches were applied to study the cellular and synaptic structure of the rat dorsal vagal nucleus (DVN). The cellular organization of the DNV does not allow one to distinguish any subnuclei, but the conspicious population of mostly small neurons in the lateral nucleus' rostral stretch lacking AChE activity. DVN neurons with high and moderate AChE activities were evident on the 5th postnatal day. Their number increased on day 7. In this critical period of brain sex differentiation, sex dimorphism was observed in the activity of DVN cholinergic neurons. Electron microscopic studies showed a great variety of DVN patterns. The fact that in the rat DVN there are complicated synaptic structures resembling glomerules is described in the paper. Two types of synaptic glomerules were identified. The results suggest that DVN can be seen as a sex-dependent brain region involved in sufficiently high information processing.

Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus).

The efferent projections of the suprachiasmatic nucleus (SCN) in the golden hamster have been examined by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (Pha-L). SCN projections were further localized through a combination of restricted SCN-lesions and immunocytochemistry for three well-known peptidergic transmitters contained in SCN neurons, viz. vasopressin (VP), vasoactive intestinal peptide (VIP), and gastrin-releasing peptide (GRP). Thus, major terminal fields of SCN-derived VP were detected in the medial preoptic nucleus, the anterior part of the paraventricular nucleus of the thalamus (PVA), the medial parvicellular part of the paraventricular nucleus of the hypothalamus (PVN), and the medial part of the dorsomedial nucleus of the hypothalamus (DMH). VIP-containing projections from the SCN were discovered in the PVA, anterior and dorsal parvicellular divisions of the PVN, subparaventricular area, and medial DMH. Efferent fibers from the SCN containing GRP were restricted to the subparaventricular area, medial DMH, and supraoptic nucleus. In addition, Pha-L tracing indicated the existence of SCN projections which could not be ascribed to one of the presently investigated peptides. Furthermore, a pronounced innervation of the contralateral SCN was observed, of which the neurotransmitter remains to be established. The results of the present study indicate that the different neuronal populations in the SCN, as characterized by their transmitter content, also show a clear diversity in their preferential target areas.

Spontaneous feeding-related monoaminergic changes in the rostromedial hypothalamus revealed by microdialysis.

The activity of hypothalamic monoamines in response spontaneous feeding was investigated using the in vivo technique of brain microdialysis together with the instrumental recording of feeding pattern. The simultaneous variations of dopamine (DA), serotonin (5-HT), and their respective metabolites, DOPAC and 5-HIAA, were measured in the rostromedian hypothalamus, where the probe was located between the PVN and VMH. Throughout the experiment, the changes in DOPAC followed a mirror image of those in DA: DA regularly increased, reaching its zenith within the 15-min sample collected during the meal before returning to the same level as just before the meal. Following a premeal plateau, both 5-HT and 5-HIAA increased as soon as the beginning of feeding; 5-HT reached its zenith during the meal while 5-HIAA showed a more delayed and prolonged increase. When a new meal was initiated, 60 to 70 min later, a similar monoaminergic pattern was observed again. These data suggest that building up hunger is announced by an ascending slope of DA and setting up of satiation is concomitant with a descending slope of DA. Concerning serotonergic changes, the sharp 5-HT release during the meal would be a signal of satiation (transient preabsorptive fullness) while the longer-lasting increase in 5-HIAA, reflecting 5-HT synthesis, would be associated with satiety (more persistent postabsorptive state substituting satiation). These data partially confirm and extend previous pharmacological studies as well as the findings on deprivation-induced, imposed meals. They suggest a possible causal relation between monoaminergic changes and behavioral initiatives.

[Cytoarchitecture and topography of the ventromedial hypothalamic nuclei of swine (Sus scrofa domestica)]. / Zytoarchitektur und Topographie ausgewählter Kerngebiete des ventromedialen Hypothalamus des Schweines (Sus scrofa domestica).

The topography and cytoarchitecture of nc. hypothalamicus ventromedialis, nc. hypothalamicus dorsomedialis and nc. infundibularis were descripted in the pig. The nc. hypothalamicus ventromedialis is the dominant nucleus in the tuber cinereum. The rostral pole lies caudal to the nc. hypothalamicus anterior. Its caudal pole is bounded by the nc. premamillaris and the nc. hypothalamicus ventrolateralis. Scattered neurons separate the nc. hypothalamicus ventromedialis dorsal from the nc. hypothalamicus dorsomedialis. Dorsolateral it is limited by the fornix and medial from the ventricular wall by the nc. hypothalamicus periventricularis ventralis and the nc. infundibularis. The neurons are medium-sized. They are compactly arranged at the periphery but in the centre the texture is much looser. The nc. hypothalamicus dorsomedialis is a poorly delimited nucleus in the rostral part of the medial hypothalamus. Ventral it is separated from the nc. hypothalamicus ventromedialis by a narrow relative cell free zone. The area hypothalamica rostralis limits it dorsolateral and the nc. paraventricularis dorsomedial. The caudal boundary is formed medial by the nc. periventricularis dorsalis and lateral by the fornix and the area hypothalamica lateralis. Small and medium-sized neurons predominate in this nucleus. The nc. infundibularis surrounds the infundibulum and reaches the recessus mamillaris. The two lateral parts are united at the floor of the third ventricle. Its small neurons are associated with the ependym. The topography and cytoarchitecture of the pig tuber cinereum was compared with the nuclear configuration of other Artiodactyla, Perissodactyla, Carnivora and Rodentia.