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Effect of L-glutamate, injected into the posterior hypothalamus, on blood pressure and heart rate in unanesthetized and unrestrained rats.

In unanesthetized and unrestrained rats, microinjection of L-glutamate into the posterior hypothalamus produced hypertension and tachycardia. These cardiovascular responses were mostly accompanied with behavioral excitation such as searching the cage, rearing and sniffing. The cardiovascular responses elicited by L-glutamate were attenuated by prior injection with propranolol and hexamethonium but not with glutamate diethylester, phentolamine and atropine. The behavioral responses to L-glutamate were suppressed by propranolol, hexamethonium and phentolamine. These results suggest that catecholaminergic and/or cholinergic systems in the posterior hypothalamus may be involved in the mediation of the cardiovascular and behavioral responses induced by L-glutamate.

Animals↗

Evidence for histaminergic arousal mechanisms in the hypothalamus of cat.

Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. alpha-Fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of alpha-FMH (50 micrograms/1 microliter) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 micrograms/1 microliter) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 micrograms/1 microliter), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 micrograms/1 microliter, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.

Animals↗

A comparison of the effect of preoperative gentling on the mouse killing and reactivity induced by lesions of the lateral septum, the medial accumbens nucleus, and the medial hypothalamus.

Adult male rats were either gentled or not gentled 10 min each day for 5 days and then subjected to lesions of the lateral septum, the medial accumbens, the medial hypothalamus, or were given sham lesions. Mouse killing was tested in the living cage on Days 2, 7, and 14 postoperatively while reactivity to the experimenter was tested on Days 3, 8, and 15. The frequency of killing in the gentled groups was always significantly higher than that of the gentled sham-lesion controls, but the frequency of killing by the nongentled groups was seldom significantly higher than that of the nongentled sham-lesioned controls. Gentling caused a slight enhancement of killing in the lesioned animals and a slight attenuation of killing in the sham lesioned animals. Preoperative gentling attenuated reactivity to the experimenter in animals with lesions of the lateral septum but not in those with lesions of the medial accumbens nucleus or the medial hypothalamus. The observation that preoperative gentling tends to increase mouse killing confirms previous observations. The finding that preoperative gentling attenuates reactivity following septal but not medial accumbens or medial hypothalamic lesions suggests that these structures subserve different functions in the inhibitory modulation of defensive behavior.

Animals↗

D-glucose infusions into the basal ventromedial hypothalamus and feeding.

Following symmetrical bilateral infusion of D-glucose into the basal ventromedial hypothalamus (BVMH), using Alzet minipumps (1 microliter/h of 10% D-glucose for 6 days), average daily food intake was reduced by 27% for the period of treatment. Symmetrical bilateral infusions into the posterior medial hypothalamus had a transitory effect on feeding, as did asymmetrical and unilateral infusions. Infusion of L-glucose into the BVMH did not yield a chronic reduction in food intake. Included in the infused solutions were tracer amounts of [14C]glucose, [14C]proline or [14C]leucine to permit radioautographic estimations of infusate dispersal in the brain and axonal transport patterns from the infusion sites. Infusions were generally well-restricted to 1-1.5 mm of the cannulae tips, and descending transport of amino acids was highest in substantia nigra and midline structures of the mesencephalon and pons including central gray, ventral tegmental area, raphe and ventral tegmental nuclei. These results provide evidence for an energy intake regulatory mechanism situated in the BVMH whose outputs may modulate activity in the substantia nigra and midline brain stem areas.

Animals↗

Kainic acid lesions of the cat's antero-medial hypothalamus and emotional-defensive response evoked by carbachol injection to the same loci.

Injections of carbachol (CCh) through a chronic cannula into the antero-medial hypothalamus (AMH) of the cat induced the emotional-defensive response (EDR) which was evaluated by time duration and number of growls in a 30-min experimental session. That response was examined before and after injection of kainic acid (KA) to the same loci of hypothalamus. None of KA doses employed (3 micrograms/2 microliter and 6 micrograms/2 microliter of vehicle) brought about statistically significant changes in parameters of the vocal response. The results suggest that either the AMH neuronal perikarya responsible for CCh-induced EDR, are resistant to KA, or muscarinic receptors initiating the EDR are not localized on perikarya.

Aggression↗

Immunocytochemical demonstration of DSIP-like immunoreactivity in the hypothalamus of the rat.

The distribution of delta sleep-inducing peptide immunoreactivity (DSIP-IR) was studied in the rat diencephalon. Varicose nerve fibers exhibiting DSIP-IR were found throughout the mediobasal hypothalamus, most frequently in the hypothalamic arcuate nucleus and in the adjoining median eminence and pituitary stalk. This innervation provides a basis for the involvement of DSIP in neuroendocrine regulation at the hypothalamic level. In the hypothalamus, DSIP-IR innervation was also observed close to the third ventricle and within the mamillary complex. Despite pretreatment with colchicine, no evidence of immunoreactive cell bodies containing DSIP-IR could be found.

Animals↗

In vitro effects of a synethetic enkephalin analogue (D-Met2,Pro5)-enkephalinamide on the hypothalamus-pituitary--testis function in rats.

The effects of (D-Met2,Pro5)-enkephalinamide, a synthetic analogue of the natural opioid pentapeptides, were investigated on the hypothalamus-pituitary-testis axis using in vitro tissue and isolated cell incubation systems. (D-Met2,Pro5)-enkephalinamide in a concentration range 10(-7)--10(-5) M did not alter the testosterone production and the troph-hormone sensitivity of the isolated Leydig cells, or the gonadotroph hormone release and the luteinizing-hormone--releasing hormone (LH-RH) sensitivity of the isolated anterior pituitary cells. However 10(-5)--10(-5) M synthetic enkephalin analogue induced a dose-dependent inhibition of LH-RH content and release of the mediobasal hypothalamus, which was prevented by equimolar concentrations of naloxone.

Animals↗

Superior colliculus efferents to the hypothalamus.

The projection of the superior colliculus to the hypothalamus was studied in the rabbit and rat with light and electron microscopic techniques. This projection system, as demonstrated with the anterograde transport of tritiated leucine, proline, adenosine or horseradish peroxidase, is primarily to dendrites located in the ipsilateral optic and supraoptic tracts. The dendrites originate from cells located in the lateral and anterior hypothalamic areas, retrochiasmatic area and supraoptic nucleus. Thus, the ventral tier of the hypothalamus appears to receive both separate and overlapping visual and multimodal sensory-motor inputs from the retina, ventral lateral geniculate nucleus and superior colliculus.

Adenosine↗

Immunohistochemical localization of corticotropin-releasing factor (CRF)-like immunoreactivity in the hypothalamus of the newt, Triturus cristatus.

The distribution of corticotropin-releasing factor (CRF) immunoreactivity was investigated in the hypothalamus and preoptic area of the newt by single and double immunocytochemical procedures. CRF immunopositive cell bodies were seen in the preoptic area (from the anterior wall of the preoptic recess to the dorsal parts of the preoptic nucleus) and in the tuberal portions of the posterior hypothalamus. Abundant nerve fibres are seen in the outer zone of the median eminence, while the pars nervosa lacks CRF-immunoreactivity. CRF immunoreactive material is seemingly separated from neurophysins- and somatostatin immunoreactive cell bodies and fibres.

Animals↗

The effects of pregnancy and parturition on the levels of substance P-like immunoreactivity in different areas of the hypothalamus.

1. The concentrations of substance P-like immunoreactivity (SPLI) have been measured in the rostral and caudal areas of the hypothalamus of male rats and of virgin, pregnant and puerperal female rats. 2. The rostral:caudal ratio of SPLI is similar in males and virgin females, but diminishes in pregnancy and decreases further during the puerperium. In the pre-optic area, the SPLI concentration fell significantly during parturition, from 241.8 to 177.2 pmols/g wet weight (P < 0.05), and in the medio-basal hypothalamus, the concentration rose during pregnancy and parturition, from 87.4 to 145.5 pmols/g wet weight (P < 0.001). 3. The results are discussed in relation to the endocrine and nociceptive aspects of pregnancy and parturition.

Animals↗

The connections between the septum-diagonal band complex and histaminergic neurons in the posterior hypothalamus of the rat. Anterograde tracing with Phaseolus vulgaris-leucoagglutinin combined with immunocytochemistry of histidine decarboxylase.

The connections between nuclei of the septum-diagonal band complex and the clusters of histaminergic neurons in the posterior hypothalamic region were studied with a dual-labeling procedure in which anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin was combined with immunohistochemistry of histidine decarboxylase. Phaseolus vulgaris-leucoagglutinin was injected in the medial and lateral septal nuclei, and in various parts of the nuclei of the diagonal band of Broca. The fibers arising from the medial and lateral septal nuclei traverse the vertical limb of the diagonal band and, in part, join the medial forebrain bundle in the preoptic area. Other fibers descend diffusely through the lateral hypothalamus to the posterior hypothalamus, or course in a bundle of fibers ensheathing the fornix. The nuclei of the diagonal band project via the medial forebrain bundle and the diffuse pathway to the posterior hypothalamic region. All the nuclei of the septum-diagonal band complex, with the exception of the medial and lateral parts of the nucleus of the horizontal limb of the diagonal band, project to clusters of histaminergic neurons. These projections exhibit the following arrangement: along the axis lateral septal nucleus-medial septal nucleus-vertical limb of the diagonal band-medial part of the horizontal limb of the diagonal band, the septohypothalamic fibers decrease in density and distribute to fewer clusters of histaminergic neurons. Varicosities on the labeled fibers are formed in close proximity to the cell bodies and dendrites of the histaminergic neurons.

Animals↗

The influences of hyperosmolality and synaptic inputs on galanin and vasopressin expression in the hypothalamus.

Galanin is a neuropeptide that is widely distributed throughout the rat central nervous system. It is co-localized with vasopressin in magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. Vasopressin biosynthesis is increased there by various hyperosmolar stimuli, including drinking 2% saline. We previously demonstrated that the chronically hyperosmolar Brattleboro rat has increased biosynthesis of galanin in the paraventricular and supraoptic nuclei. In this report we show using hybridization histochemistry that drinking 2% saline also increased galanin transcripts in these nuclei. We also demonstrate using hybridization histochemistry and immunohistochemistry that knife cuts that sever hypothalamo-hypophysial fibers transiently elevated galanin expression in the supraoptic nucleus ipsilateral to the lesion and depressed vasopressin expression ipsilaterally. Pituitary stalk transections also elevated galanin and decreased vasopressin transcripts. In addition, various knife cuts in the caudal hypothalamus were able to dissociate the expression of vasopressin and galanin, although co-localized and similarly affected by hyperosmolality in the supraoptic nucleus. Unilateral sagittal knife cuts that divided the posterior hypothalamus but avoided the hypothalamo-hypophysial pathway, as well as hemisections at the level of the premammillary area, resulted in ipsilateral elevations of galanin transcripts without significantly affecting vasopressin expression. These results indicate that independent intracellular signal transduction pathways exist for regulating expression of the two genes.

Animals↗

Electron microscopic effects of thallium poisoning on the rat hypothalamus and hippocampus: biochemica changes in the cerebrum.

Rats were given thallous acetate (5 mg elemental thallium/kg body weight) IP daily for 7 days and prepared for electron microscopy (perfusion-fixation) and for biochemical study. Increased incidence of Golgi zones and electron-dense bodies were observed in the anterior hypothalamus and hippocampus. Sequestrated axons were seen in the hypothalamus. Depletion of succinic dehydrogenase and guanine deaminase occurred in the cerebrum.

Animals↗

Sagittal knife cuts in the far-lateral hypothalamus reduce sexual receptivity in female hamsters.

We have previously shown that hypothalamic knife cuts confined to the sagittal plane lateral to the medial anterior hypothalamus-ventromedial nucleus can disrupt sexual receptivity in female golden hamsters. In the present study we have compared the effects of varying the lateral position of sagittal cuts located at this same rostral-caudal level. Near-lateral (NL) cuts were placed at or just lateral to the fornix, while far-lateral (FL) cuts were placed at the lateral edge of the medial forebrain bundle. Ovariectomized, estradiol benzoate plus progesterone-treated females were given weekly tests for lordosis before and after hypothalamic cuts. Changes in body weight and agonistic behavior were also recorded. Both NL and FL cuts reduced lordosis in response to both manual stimulation and a sexually active male. Postoperatively, it was more difficult to elicit lordosis from these females, and if elicited, the duration of the response was reduced. NL, but not FL, cuts also increased agonistic behavior, and produced obesity. Since both NL and FL cuts severed axons traveling in the region of the supraoptic commissures (SOC), these data support our hypothesis that these SOC connections are critical for sexual receptivity. The SOC carrys both efferents and afferents of the ventromedial hypothalamus. Sagittal-plane cuts which interrupt the SOC may disrupt lordosis by cutting either or both types of connection.

Agonistic Behavior↗

Influence of preoptico-anterior and posterior hypothalamus on midline thalamic neurons.

The present study was aimed at understanding the influence of the posterior hypothalamus (PH) and the preoptico-anterior hypothalamus (PO-AH) on the neurons of the midline thalamus (MTh) in encéphale isolé cats. A majority of the influenced neurons of the MTh showed increased firing on stimulation of the PH. Although the number of neurons showing increased or decreased firing on PO-AH stimulation were nearly equal, stimulus bound increased firing in many neurons was followed by a prolonged decreased firing. It is likely that the hypothalamo-thalamic circuit constitutes a parallel pathway to the reticulo-thalamic circuit for alteration of the cortical EEG.

Action Potentials↗

A direct hepatic osmoreceptive afferent projection from nucleus tractus solitarius to dorsal hypothalamus.

Thirty units that responded antidromically to electrical stimulation of the zona incerta (ZI) or the dorsal portion of hypothalamus were recorded in the nucleus tractus solitarii (NTS). These units were analyzed in relation to hepatoportal afferent inputs. Electrical stimulation of the hepatic branch of the vagus nerve facilitated six units (facilitatory units) and suppressed 10 units (suppressed units). Effect of the portal infusion of hypertonic saline was examined on six facilitatory and eight suppressed units. One facilitatory unit and one suppressed unit increased their discharge rates in response to portal infusion. Four facilitatory units and one suppressed unit decreased their discharge rates in response to the same stimulation. Increased or decreased discharge rates in response to portal infusion of hypertonic saline were observed in units that responded antidromically to electrical stimulation of the paraventricular hypothalamic nucleus, the lateral hypothalamic area, or the ZI. It is concluded that hepatoportal osmoreceptive signals are conveyed to the hypothalamus or the ZI directly from the NTS.

Afferent Pathways↗

Role of the hypothalamus in insulin-independent glucose uptake in peripheral tissues.

To clarify the role of the ventromedial hypothalamus (VMH)-sympathetic nervous system in insulin-independent glucose uptake in peripheral tissues, tissue glucose uptake was assessed in vivo by the 2-[3H]deoxyglucose method during electrical stimulation of the VMH in anesthetized rats. VMH stimulation significantly increased the rate constant of glucose uptake in brown adipose tissue (BAT), heart and skeletal muscles, but not in white adipose tissue and brain. The effect of VMH stimulation on glucose uptake in BAT was abolished by local sympathetic denervation, indicating that the increase in glucose uptake is mediated by the sympathetic nerves. Electrical stimulation of the lateral hypothalamus, on the other hand, had no appreciable effects on 2-[3H]deoxyglucose uptake in any tissues. Changes in glucose transporters after VMH stimulation were also examined by the [3H]cytochalasin B binding method using sarcolemmal membranes isolated from heart muscle. Scatchard analysis of cytochalasin B binding indicated that VMH stimulation did not alter both the number and affinity (dissociation constant) of glucose transporters in the heart sarcolemmal membranes, whereas insulin administration increased the number of transporters in the membranes. These results suggest that the mechanism by which VMH stimulation increases glucose uptake in muscle is different from that of insulin.

Animals↗

Amygdala enterostatin induces c-Fos expression in regions of hypothalamus that innervate the PVN.

Enterostatin selectively inhibits the intake of the dietary fat after both central and peripheral administration. Our previous studies have shown that a central site of action is the central nucleus of amygdala. Serotonergic agonists administered into the paraventricular nucleus (PVN) inhibit fat intake and serotonergic antagonists block the feeding suppression induced by amygdala enterostatin, suggesting that there are functional connections between the PVN and amygdala that affect the feeding response to enterostatin. Our purpose was to identify the anatomic and functional projections from the amygdala to the PVN and hypothalamic area that are responsive to enterostatin, by using a retrograde tracer fluorogold (FG) and c-Fos expression. Rats were injected with fluorogold unilaterally into the PVN and a chronic amygdala cannula was implanted ipsilaterally. After 10 days recovery, rats were injected with either enterostatin (0.1 nmol) or saline vehicle (0.1 microl) into the amygdala and sacrificed 2 h later by cardiac perfusion under anesthesia. The brains were subjected to dual immunohistochemistry to visualize both FG and c-Fos-positive cells. FG/c-Fos double-labeled cells were found in forebrain regions including the PVN, amygdala, lateral hypothalamus (LH), ventral medial hypothalamus (VMH) and arcuate nucleus (ARC). The data provides the first anatomical evidence that enterostatin activates amygdala neurons that have functional and anatomic projections directly to the PVN and also activates neurons in the arcuate, LH and VMH, which innervate the PVN.

Amygdala↗