Cholinergic stimulation in the posterior hypothalamic nucleus activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats (SHR). Acetylcholine in the posterior hypothalamic nucleus (PHN) has been implicated in hypertension in SHR. It is suggested that there exist neuronal projections from the PHN to the AHA in rats. In this study, we examined whether cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol, physostigmine and glutamate into the PHN caused an increase in firing rate of AHA angiotensin II-sensitive neurons in anesthetized rats. The carbachol-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was also inhibited by the pressure application of losartan. PHN microinjections of carbachol and glutamate did not affect blood pressure in these anesthetized rats. In conscious rats, PHN microinjection of carbachol produced an increase of blood pressure and the carbachol-induced pressor response was inhibited by bilateral microinjections of losartan into the AHA. These findings indicate that cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by PHN cholinergic stimulation is partly mediated via release of angiotensins at AHA angiotensin II-sensitive neuron levels.     

Efferents from the medial anterior hypothalamic area in the guinea pig

Medial anterior hypothalamic connections were studied with H³-proline and autoradiography. Most of the axons projected to other hypothalamic nuclei. The major pathways were found ventral medial to the fornix and in the periventricular tract. Substantial projections were apparent in the ventromedial and dorsomedial nuclei with less label in the arcuate nucleus. The dorsal premammillary nuclei were labeled bilaterally, particularly with more caudal injections of anterior hypothalamus. Efferents were evident in the posterior hypothalamus and continued into the central gray of the midbrain. Labeled fibers reached the ventral tegmental area and in the reticular formation were traced only through pons. Rostral projections were to the medial and lateral preoptic areas and ventral lateral septum. The bed nucleus of stria terminalis was labeled and a very few fibers reached the medial amygdaloid nucleus. The periventricular nucleus of thalamus was labeled.     

Morphology of neurons in the anterior hypothalamic area and supraoptic hypothalamic nucleus of the adult human brain

Morphological features of neuronal cell types in the anterior hypothalamic area (AHA) and supraoptic hypothalamic nucleus (SON) of the adult human brain were analysed in Golgi impregnated preparations. Four neuronal cell types were described for the first time in these human nuclei. Type I neurons were found in both the AHA and SON, while the other three cell types (types II–IV) were found only in the SON. Type I neurons had elongated, triangular or multipolar somata, which emitted 2–5 sparsely branching primary dendrites with a moderate number of fine spines. Also many of type I neurons in the AHA had thin dendritic side-branches. Type II neurons had round or fusiform somata, and two occasionally branching primary dendrites. Type III neurons were multipolar neurons with 3–5 densely spined and sparsely branching dendrites. Their axons had collaterals. Type IV neurons had very small ovoid somata with one smooth and unbranched primary dendrite. The neurons in the human AHA and SON were similar to those observed in the same areas in other mammalian species, except for the very small neurons in the SON and the thin dendritic side-branches of type I neurons in the AHA, that had not been previously described.

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Sommario Sono state analizzate le caratteristiche morfologiche delle popolazioni cellulari impregnate con metodo di Golgi, nelle aree ipotalamiche anteriore (AHA) e sopraottica (SON) del cervello umano adulto. Per la prima volta vengono descritte quattro sottopopolazioni neuronali. I neuroni del tipo I sono stati osservati sia in AHA che in SON mentre gli altri tre sottotipi neuronali (tipi II – IV) sono stati trovati solo in SON. I neuroni di tipo I hanno soma allungato, triangolare o multipolare da cui emergono 2–5 dendriti primari con un numero ridotto di spine. Molti di questi neuroni in AHA hanno sottili ramificazioni dendritiche. I neuroni di tipo II presentano un soma tondeggiante o fusiforme e generalmente due ramificazioni dendritiche principali. Il tipo III è caratterizzato da neuroni multipolari con 3–5 ramificazioni dendritiche ricche di spine. I loro assoni presentano collaterali. Il tipo IV ha soma piccolo ed ovoidale con dendriti primari sottili e che non si ramificano. I neuroni osservati nei nuclei AHA e SON dell'uomo sono simili a quelli osservati nelle stesse aree di altre speci animali ad eccezione dei piccoli neuroni in SON e delle caratteristiche delle ramificazioni dendritiche dei neuroni di tipo I in AHA. Queste caratteristiche morfologiche non sono state precedentemente descritte.

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This study was supported by Jordan University of Science and Technology Grant No. 13/94.     

下丘脑前核：参与褪黑素对血压影响的中枢部位

在大鼠用微量注射技术研究褪黑素在下丘脑前核对心血管活动的作用 ,以及用辣根过氧化物酶神经传导通路追踪技术研究下丘脑前核参与心血管活动交感传出的纤维投射。结果表明 ,下丘脑前核微量注射褪黑素可使血压呈剂量依赖性降低 ,下丘脑前核有大量纤维投射到室旁核、正中隆起、下丘脑腹内侧核、弓状核、中脑导水管周围灰质 ,有少量纤维投射到延髓腹外侧区、中缝隐核。因此 ,褪黑素可能为一种降压因子 ,下丘脑前核是褪黑素调节心血管活动的重要中枢部位之一 ,而且下丘脑前核可能通过下丘脑腹内侧核、弓状核、中脑导水管周围灰质、延髓腹外侧区和中缝隐核来影响心血管交感传出活动     

下丘脑前核:参与褪黑素对血压影响的中枢部位

在大鼠用微量注射技术研究褪黑素在下丘脑前核对心血管活动的作用,以及用辣根过氧化物酶神经传导通路追踪技术研究下丘脑前核参与心血管活动交感传出的纤维投射.结果表明,下丘脑前核微量注射褪黑素可使血压呈剂量依赖性降低,下丘脑前核有大量纤维投射到室旁核、正中隆起、下丘脑腹内侧核、弓状核、中脑导水管周围灰质,有少量纤维投射到延髓腹外侧区、中缝隐核.因此,褪黑素可能为一种降压因子,下丘脑前核是褪黑素调节心血管活动的重要中枢部位之一,而且下丘脑前核可能通过下丘脑腹内侧核、弓状核、中脑导水管周围灰质、延髓腹外侧区和中缝隐核来影响心血管交感传出活动.     

Responses of rat lateral hypothalamic neuron activity to vestibular nuclei stimulation

Effects of lateral vestibular nucleus (LVN) stimulation on neuronal activity in the rat lateral hypothalamic area (LHA), including specific glucose-sensitive neurons, were investigated by extracellular and intracellular recordings in vivo. Stimulation of the contralateral LVN evoked 3 types of response in 46% (111/240) of the neurons recorded extracellularly: long latency (38.1 +/- 23.6 ms) excitation (62/111, 56%), short latency (6.9 +/- 3.1 ms) excitation-inhibition (33/111, 30%), and inhibition with 20.1 +/- 11.1 ms latency (16/111, 14%). Glucose-sensitive neurons, which were identified by electrophoretic application of glucose, did not respond specifically to such stimulation. Neuronal activity was recorded intracellularly from 31 LHA neurons, of which 13 responded to LVN stimulation. Seven of the 13 neurons showed a long latency EPSP (10.4 +/- 5.5 ms) and the remaining 6 exhibited an EPSP-IPSP sequence with shorter latency (4.5 +/- 3.0 ms). The amplitude of these responses was graded with a change in stimulus intensity. The EPSPs of both types of response were considered to be polysynaptic because of shortening of latencies by higher current stimulation. Since the LHA is implicated in the regulation of autonomic nerve activity, the present results showing polysynaptic pathways from the LVN to the LHA suggest functional involvement of the LHA in vestibulo-autonomic responses.     

Lateral hypothalamic area stimulation excites neurons in the region of the subfornical organ with efferent projections to the hypothalamic paraventricular nucleus in the rat

Fifteen neurons in the region of the subfornical organ (SFO) were antidromically activated by electrical stimulation of the paraventricular nucleus (PVN) in the rat. Electrical stimulation of the lateral hypothalamic area (LHA) excited the activity of 9 of the identified units, but did not affect the remaining units. The excitatory response of the identified units was blocked by microiontophoretically (MIPh) applied saralasin (Sar), an angiotensin II (ANGII) antagonist, but not by atropine (Atr), a muscarinic antagonist. These results suggest that the LHA has an excitatory influence on the activity of neurons in the region of the SFO with efferent projections to the PVN and that the influence may be mediated by ANGII receptors.     

Angiotensin receptor blockade in the anterior hypothalamic area inhibits stress-induced pressor responses in rats

Central angiotensin systems are involved in expression of pressor responses induced by immobilization stress. In this study, we examined whether angiotensin receptors in the anterior hypothalamic area are involved in the pressor response during stress exposure in rats. Intracerebroventricular injections of the angiotensin AT1-receptor antagonist losartan (6.5 and 22 nmol) attenuated pressor responses to immobilization stress dose-dependently. Injections of losartan (0.065 and 0.22 nmol) into the anterior hypothalamic area also suppressed the stress-induced pressor response dose-dependently, whereas intraventricular injection of losartan (2.2 nmol) did not affect it. Immobilization stress caused increases in plasma catecholamine levels. The stress-induced increase of plasma catecholamine levels was also inhibited by angiotensin receptor blockade in the anterior hypothalamic area. The present results suggest that angiotensin receptors in the anterior hypothalamic area are involved in expression of the pressor response and sympathetic activation induced by immobilization stress.     

Sexual dimorphism in the preoptic/anterior hypothalamic area of ferrets: Effects of adult exposure to sex steroids

The organization of neuronal cell bodies in the caudal preoptic area (POA) and rostral anterior hypothalamic area (AH) was studied in Nissl-stained brain sections from adult male and female ferrets. Computer-assisted image-analysis procedures were developed to help estimate the areas of cellular density and the sizes of individual perikarya. At the junction of the POA and AH, a bilateral dorsal-medial group of neurons was apparent only in male ferrets (dorsal nucleus). At the same coronal level, a ventral-medial group of neurons was apparent bilaterally in both males and females (ventral nucleus). The mean somal area of cells in the dorsal nucleus of males was significantly greater than the mean somal area of cells in the corresponding dorsal region of females or in the ventral nucleus of both sexes. The dorsal nucleus was clearly discernible in adult males regardless of their hormonal status, although cells in the dorsal nucleus were larger in intact breeding males or gonadectomized males given testosterone, estradiol or dihydrotestosterone than in gonadectomized males given no gonadal hormones or given progesterone. Neither the grouping of large cells nor the steroid-induced increase in cell size, characteristic of the male dorsal nucleus, was seen in the comparable dorsal region of females. The sex difference in cellular organization observed in the ferret at the junction of the POA and AH is the first difference of this type to be seen in the POA/AH of a non-rodent mammalian species. Its identification will, hopefully, aid in the analysis of the neural mechanisms that control various sex-specific behaviors in this species.     

Facilitation of baroreflex-induced bradycardia by stimulation of specific hypothalamic sites in the rat

Hypothalamic stimulation generally inhibits baroreflex-induced bradycardia. However, we have noted discrete areas of the rat hypothalamus which facilitate reflex bradycardia. The effects of hypothalamic stimulation on baroreflex-induced changes in heart rate were investigated in urethane-anesthetized rats (1.2 g/kg, i.p.; n = 6) instrumented with femoral arterial and venous catheters. Bipolar electrodes (250 micron diameter) were implanted stereotaxically in the hypothalamus. Baroreflex-induced bradycardia was elicited by phenylephrine (PE) injection (8-20 micrograms/kg). Responses to stimulation (STIM) (50-150 microA, 80 Hz, 0.5 ms), PE, and Stim + PE were studied for 1 min. In the ventral medial and anterior hypothalamus, STIM caused transient increases in blood pressure and no changes in heart rate. Peak blood pressure was lower during STIM + PE than during PE (144 +/- 5 vs 164 +/- 3 mm Hg; P less than 0.05). However, STIM + PE resulted in a lower heart rate compared to PE (194 +/- 22 22 vs 270 +/- 17 bpm; P less than 0.05). At 1 min, the heart rate in STIM + PE rats remained lower than in PE rats (205 +/- 37 vs 319 +/- 16 bpm; P less than 0.05). Atropine administration indicated that the facilitation was primarily parasympathetic in nature. These results identify specific hypothalamic regions which facilitate baroreflex-induced bradycardia by parasympathetic mechanisms.     

Efferent connections of the lateral hypothalamic area of the rat: An autoradiographic investigation

The efferent projections of the lateral hypothalamic area (LHA) at mid-tuberal levels were examined with the autoradiographic tracing method. Connections were observed to widespread regions of the brain, from the telencephalon to the medulla. Ascending fibers course through LHA and the lateral preoptic area and lie lateral to the diagonal band of Broca. Fibers sweep dorsally into the lateral septal nucleus, cingulum bundle and medial cortex. Although sparse projections are found to the ventromedial hypothalamic nucleus, a prominent pathway courses to the dorsal and medial parvocellular subnuclei of the paraventricular nucleus. Labeled fibers in the stria medullaris project to the lateral habenular nucleus. The central nucleus of the amygdala is encapsulated by fibers from the stria terminalis and the ventral amygdalofugal pathway. The substantia innominate, nucleus paraventricularis of the thalamus, and bed nucleus of the stria terminalis also receive LHA fibers. Three descending pathways course to the brainstem: (1) periventricular system, (2) central tegmental tract (CTT), and (3) medial forebrain bundle (MFB). Periventricular fibers travel to the ventral and lateral parts of the midbrain central gray, dorsal raphe nucleus, and laterodorsal tegmental nucleus of the pens. Dorsally coursing fibers of CTT enter the central tegmental field and the lateral and medial parabrachial nuclei. The intermediate and deep layers of the superior colliculus receive some fibers. Fibers from CTT leave the parabranchial region by descending in the ventrolateral pontine and medullary reticular formation; some of these fibers sweep dorsomedially into the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and nucleus commissuralis. From MFB, fibers descend into the ventral tegmental area and to the border of the median raphe and raphe magnus nuclei.     

Effect of cortical masticatory area stimulation on swallowing in anesthetized rabbits

The effects of stimulation of the cortical masticatory area (CMA) on swallowing evoked by superior laryngeal nerve (SLN) were studied in anesthetized rabbits. Electromyographic activity of the thyrohyoid, masseter, and digastric muscles and jaw-movement trajectories were recorded to monitor rhythmic jaw movements (RJMs) or swallowing. A systematic series of microelectrode penetrations within the CMA was made for each animal, and the effects of CMA stimulation on swallowing were tested by comparing the number of swallows evoked by stimulation of the CMA alone, the SLN alone, and simultaneous stimulation of the SLN and CMA. A significant facilitatory effect was observed in 49 (52%) of the 95 CMA loci tested. No significant effect was noted in the remaining 46 loci. Three different types of RJMs were evoked by CMA stimulation, and topographical organization was noted among CMA loci that evoked different types of RJMs. A high percentage of (77%) the CMA loci that evoked RJMs with a prominent horizontal excursion of the jaw facilitated swallowing and was located in the posterolateral and deep part of the CMA. A majority (88%) of the CMA loci that evoked RJMs with small circular jaw movements did not affect swallowing and was located in the anteromedial and shallow part of the CMA. The facilitatory effect of CMA stimulation on swallowing remained even after removal of peripheral sensory inputs by means of deafferentation of infraorbital and inferior alveolar nerves. Results suggest the existence of facilitatory descending pathways to the swallowing center from particular intracortical loci of CMA.     

辣椒素对大鼠膀胱内压及CGRP—，NPY—免疫反应性神经的影响

观察了不同浓度的辣椒素 (CAP)注入大鼠膀胱后 ,膀胱内压、膀胱容量的泌尿动力学变化及CAP对膀胱壁内含CGRP及NPY免疫反应性 (IR)神经的影响。结果发现 ,高浓度CAP(4mmol/L及 8mmol/L)处理后膀胱最大压力明显下降 ,而膀胱容量及残余尿量增加 (P 0 .0 1)。免疫组织化学发现 ,各种浓度的CAP均明显降低膀胱壁各层CGRP IR神经纤维的长度和密度 (P 0 .0 0 1)。结果表明 ,CAP能广泛耗竭膀胱组织内CAP敏感的一级传入神经末梢中的CGRP ,并表现出一定的浓度依赖性变化 ,此可能为降低膀胱内压 ,引起尿潴留和充溢性尿失禁的神经原性病理机制。这可能为临床上局部使用CAP治疗神经原性膀胱 (逼尿反射亢进 )、缓解尿频尿急提供理论依据     

Identification of retinal ganglion cells projecting to the lateral hypothalamic area of the rat

The objective of the present study was to identify the retinal ganglion cells projecting to the lateral hypothalamic area of the rat. The retinohypothalamic tract has been divided into a medial and a lateral component on anatomical and developmental grounds. The medial component projects to the suprachiasmatic nucleus and adjacent structures such as the anterior hypothalamic and retrochiasmatic areas. The lateral component terminates in the lateral hypothalamic area dorsal to the supraoptic nucleus. Injections of the retrograde tracer FluoroGold were made into the retinorecipient region of the lateral hypothalamic area and retinal whole mounts were immunohistochemically processed for retrogradely labeled retinal ganglion cells. With FluoroGold injections confined to the lateral hypothalamic area, retrogradely labeled retinal ganglion cells are located almost exclusively in the superior temporal quadrant of the retina. Their size and morphology indicates that they are a homogenous subset of type III cells, but a definitive classification would require a more complete fill of dendritic arbors than is available in our retrograde material. In contrast, injections involving fibers of passage in the optic tract, or centered in the medial terminal nucleus of the accessory optic system, label cells distributed across the entire retinal surface. Unlike the retinal ganglion cells projecting to the suprachiasmatic nucleus [Moore et al., J. Comp. Neurol., 352 (1995) 351–366], the cells labeled after restricted lateral hypothalamic injections are not distributed evenly across the retinal surface. The difference in location of the retinal ganglion cells projecting to the lateral hypothalamic area supports the view that this retinohypothalamic projection is anatomically and functionally distinct from the projection to the suprachiasmatic nucleus and adjacent medial hypothalamus.     

A comparison of the effects of electrical stimulation of the lateral and ventromedial hypothalamus on the activity of neurons in ventral tegmental area and substantia nigra

Extracellular unit recordings were obtained from neurons in the ventral tegmental area (VTA), the substantia nigra, zona compacta (SNC) and zona reticulata (SNR) of adult female albino rats anaesthetized with urethane and chloral hydrate. Neurons were divided into two types based on their electrophysiological characteristics; Type I neurons had long duration action potentials (>2.6 msec) and slow discharge rates and Type II neurons had shorter duration action potentials and a wider range of discharge rates. Both types of neurons were found in the VTA and SNC, but there were only Type II neurons in the SNR. The effects of single pulse stimuli delivered to the ipsilateral ventromedial (VMH) or lateral (LH) hypothalamic areas on activities of the two types of neurons were investigated. Only a small portion of neurons in the VTA and SNC responded to VMH stimulation, but in contrast a majority of the two types of neurons in the VTA and SNC responded to LH stimulation. Most neurons in the SNR did not respond to VMH or to LH stimulation. Type II neurons in the VTA and SNC were predominantly suppressed by LH stimulation with short onset latencies (<6 msec), indicating the possibility of monosynaptic mediation. However Type I neurons in the VTA and SNC were activated and suppressed and the onset latencies of these responses were relatively longer. The high proportion of neurons of VTA and SNC responding to electrical stimulation of LH is consistent with anatomical evidence. Suppression and activation of Type I neurons in VTA and SNC suggest that the LH exerts modulatory influences on these neurons of the midbrain.     

Effect of subthalamic deep brain stimulation on the function of the urinary bladder

Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic deep brain stimulation has a significant and urodynamically recordable effect leading to a normalization of pathologically increased bladder sensibility.     

Adrenoceptors in the preoptic-anterior hypothalamic area stimulate secretion of prolactin but not growth hormone in the male rat

Plasma growth hormone (GH) and prolactin concentrations were measured by radioimmunoassay in unanesthetized male rats after stereotaxic microinjection of adrenergic agents and 6-hydroxydopamine into the preoptic-anterior hypothalamic area (PO/AHA). Norepinephrine, epinephrine, isoprenaline and clonidine failed to stimulate GH, moreover, 16 nanomoles norepinephrine produced a decrease. However, these agents stimulated prolactin secretion and the mixed alpha antagonist phentolamine, administered systemically, inhibited the stimulatory action of epinephrine on prolactin secretion. GH and prolactin secretory patterns were not affected by 6-hydroxydopamine disruption of catecholamine terminals in the PO/AHA. GH responses to adrenergic agonists and the failure of 6-hydroxydopamine to affect GH secretory patterns indicate that PO/AHA norepinephrine afferents do not facilitate GH secretion. Taken in conjunction with previous studies, the results suggest that there must be an extra-hypothalamic site at which norepinephrine is stimulatory for GH. Prolactin responses suggest that alpha adrenoceptors in the PO/AHA may participate in prolactin secretion.     

Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat

The lateral preoptic and lateral hypothalamic regions contain the majority of the cell groups embedded in the fibre trajectories of the medial forebrain bundle on its course through the hypothalamus. Recent studies have extended considerably the parcellation of the lateral hypothalamic region, and, therefore, the need to emphasize new insights into the anatomical organisation of projections from the neurons of the lateral hypothalamic region. In the present study we describe the anatomical organisation of efferent projections from the lateral preoptic and lateral hypothalamic regions to the hypothalamic paraventricular nucleus (PVN) on the basis of retrograde- and anterograde-tracing techniques. Iontophoretic injections of the retrograde tracer, cholera toxin subunit B, into the PVN revealed that most hypothalamic nuclei project to the PVN. Within the lateral hypothalamic region, retrogradely labelled cells were concentrated in the intermediate hypothalamic area, the lateral hypothalamic area, and the perifornical nucleus, whereas fewer retrogradely labelled cells were found in the lateral preoptic area. To determine the distribution of terminating fibres in subnuclei of the heterogeneous PVN, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast, neurons of the rostral and tuberal parts of the lateral hypothalamic area and the perifornical nucleus projected to the PVN subnuclei, which contained parvicellular neurons that send descending projections to preganglionic cell groups in the medulla and spinal cord. The perifornical nucleus was the only area within the lateral hypothalamic region that consistently innervated magnocellular perikarya of the PVN. Finally, all areas of the lateral hypothalamic region contributed substantially to fibres terminating in the perinuclear shell of the PVN. These results demonstrate that anatomically distinct areas of the lateral hypothalamic region have distinct projections to subnuclei of the PVN and further substantiate the view that the lateral hypothalamic region as well as the PVN constitute anatomically and functionally heterogeneous structures. © 1994 Wiley-Liss, Inc.