Vasopressin Neurons Research Articles

Traitement du diabète insipide en 1999

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80–90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

The neurotensinergic synaptic innervation of vasopressin containing neurons in the rat hypothalamic paraventricular nucleus

A recent physiological report suggested that neurotensin could inhibit the vasopressin releasing from vasopressin-producing neurons in the hypothalamic paraventricular nucleus but not in the supraoptic nucleus. In the present study, the synaptic relationship between the neurotensin-like immunoreactive and vasopressin-like immunoreactive neurons has been examined using a pre-embedding double immunostaining technique in the rat hypothalamic paraventricular nucleus. At the light microscopic level, many neurotensin-like immunoreactive fibers were found near the vasopressin-like immunoreactive neurons. At the electron microscopic level, the neurotensin-like immunoreactive fibers were identified as axon terminals that made many synapses on the vasopressin-like immunoreactive perikarya and dendrites. The synapses were both asymmetrical and symmetrical. These findings of the present study suggest that the inhibitory effect of neurotensin on the vasopressin neurons in the hypothalamic paraventricular nucleus may be due to the direct synapses made by neurotensin-like immunoreactive axon terminals on the vasopressin-like immunoreactive neurons.

Functional Morphology of the Suprachiasmatic Nucleus

In mammals, the biological clock (circadian oscillator) is situated in the suprachiasmatic nucleus (SCN), a small bilaterally paired structure just above the optic chiasm. Circadian rhythms of sleep–wakefulness and hormone release disappear when the SCN is destroyed, and transplantation of fetal or neonatal SCN into an arrhythic host restores rhythmicity. There are several kinds of peptide-synthesizing neurons in the SCN, with vasoactive intestinal peptide, arginine vasopressin, and somatostatine neurons being most prominent. Those peptides and their mRNA show diurnal rhythmicity and may or may not be affected by light stimuli. Major neuronal inputs from retinal ganglion cells as well as other inputs such as those from the lateral geniculate nucleus and raphe nucleus are very important for entrainment and shift of circadian rhythms. In this review, we describe morphological and functional interactions between neurons and glial elements and their development. We also consider the expression of immediate-early genes in the SCN after light stimulation during subjective night and their role in the mechanism of signal transduction. The reciprocal interaction between the SCN and melatonin, which is synthesized in the pineal body under the influence of polysynaptic inputs from the SCN, is also considered. Finally, morphological and functional characteristics of clock genes, particularly mPers, which are considered to promote circadian rhythm, are reviewed.

Differences in the Properties of Ionotropic Glutamate Synaptic Currents in Oxytocin and Vasopressin Neuroendocrine Neurons

Oxytocin (OT) and vasopressin (VP) hormone release from neurohypophysial terminals is controlled by the firing pattern of neurosecretory cells located in the hypothalamic supraoptic (SON) and paraventricular nuclei. Although glutamate is a key modulator of the electrical activity of both OT and VP neurons, a differential contribution of AMPA receptors (AMPARs) and NMDA receptors (NMDARs) has been proposed to mediate glutamatergic influences on these neurons. In the present study we examined the distribution and functional properties of synaptic currents mediated by AMPARs and NMDARs in immunoidentified SON neurons. Our results suggest that the properties of AMPA-mediated currents in SON neurons are controlled in a cell type-specific manner. OT neurons displayed AMPA-mediated miniature EPSCs (mEPSCs) with larger amplitude and faster decay kinetics than VP neurons. Furthermore, a peak-scaled nonstationary noise analysis of mEPSCs revealed a larger estimated single-channel conductance of AMPARs expressed in OT neurons. High-frequency summation of AMPA-mediated excitatory postsynaptic potentials was smaller in OT neurons. In both cell types, AMPA-mediated synaptic currents showed inward rectification, which was more pronounced in OT neurons, and displayed Ca2+ permeability. On the other hand, NMDA-mediated mEPSCs of both cell types had similar amplitude and kinetic properties. The cell type-specific expression of functionally different AMPARs can contribute to the adoption of different firing patterns by these neuroendocrine neurons in response to physiological stimuli.

Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.

Absence of vasopressin expression by galanin neurons in the golden hamster: implications for species differences in extrahypothalamic vasopressin pathways

In golden hamsters, there is a complete absence of the small diameter vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BST) and medial amygdala (Me) which have been shown to exhibit steroid dependency and sexual dimorphism in many other rodent species. In rats, VP in the BST/Me is always colocalized with the neuropeptide galanin (GAL) and the sex difference in VP cell number appears to result from a sex difference in the number of GAL neurons which coexpress VP. Likewise, we reasoned that the species difference in extrahypothalamic VP pathways present in the golden hamster could result from a reduced coexpression of VP by GAL neurons in these regions. Here, we used in situ hybridization histochemistry to determine whether GAL mRNA expressing neurons are present in the BST and Me of golden hamsters despite the absence of VP expression in these regions. In addition, we have used slice binding and receptor autoradiography to identify specific GAL binding sites in the lateral septum, a probable target region of BST/Me neurons, and in situ hybridization to confirm that some of these binding sites correspond to the GALR1 GAL receptor subtype. Our findings indicate that the absence of VP expression in the BST/Me of golden hamsters results from a failure of extrahypothalamic GAL neurons to express the VP phenotype. Because GAL is expressed in the extended amygdaloid complex and GAL receptors are present in the septum of golden hamsters, GAL may play a role in modulating functions previously attributed to BST/Me pathways.

Central Peptidergic Neurons Are Hyperactive during Collateral Sprouting and Inhibition of Activity Suppresses Sprouting

Little is known regarding the effect of chronic changes in neuronal activity on the extent of collateral sprouting by identified CNS neurons. We have investigated the relationship between activity and sprouting in oxytocin (OT) and vasopressin (VP) neurons of the hypothalamic magnocellular neurosecretory system (MNS). Uninjured MNS neurons undergo a robust collateral-sprouting response that restores the axon population of the neural lobe (NL) after a lesion of the contralateral MNS (). Simultaneously, lesioned rats develop chronic urinary hyperosmolality indicative of heightened neurosecretory activity. We therefore tested the hypothesis that sprouting MNS neurons are hyperactive by measuring changes in cell and nuclear diameters, OT and VP mRNA pools, and axonal cytochrome oxidase activity (COX). Each of these measures was significantly elevated during the period of most rapid axonal growth between 1 and 4 weeks after the lesion, confirming that both OT and VP neurons are hyperactive while undergoing collateral sprouting. In a second study the hypothesis that chronic inhibition of neuronal activity would interfere with the sprouting response was tested. Chronic hyponatremia (CH) was induced 3 d before the hypothalamic lesion and sustained for 4 weeks to suppress neurosecretory activity. CH abolished the lesion-induced increases in OT and VP mRNA pools and virtually eliminated measurable COX activity in MNS terminals. Counts of the total number of axon profiles in the NL revealed that CH also prevented axonal sprouting from occurring. These results are consistent with the hypothesis that increased neuronal activity is required for denervation-induced collateral sprouting to occur in the MNS.

Effects of osmotic pressure and brain-derived neurotrophic factor on the survival of postnatal hypothalamic oxytocinergic and vasopressinergic neurons in dissociated cell culture.

Neurons from hypothalamic paraventricular nuclei (PVN) and supraoptic nuclei (SON) from postnatal day 6-8 rats were enzymatically dissociated and separately maintained in monolayer cultures for 14 days. The osmotic pressure of the culture medium, based on Neurobasal medium (Life Technologies), was varied (255, 300 and 330 mOsm/l) by adjustment using mannitol. The survival of oxytocin (OT), vasopressin (VP) and oxytocin-vasopressin (OT/VP) coexpressing neurons were studied under these varied conditions, and the identification of the cell phenotypes in the cultures was carried out by using double-label immunofluorescence. Under control osmolar conditions (300 mOsm/l) equivalent numbers of OT and VP neurons were found in the SON (P = 0.8398) and PVN (P = 0.4721) cultures. The OT neurons' survival did not change in 255 or 330 mOsm media in the SON cultures, but the VP neurons in the SON cultures were significantly increased in 255 mOsm/l medium as compared to control (300 mOsm/l) medium (P = 0.0088). No significant changes were found in VP neuron survival in SON cultures between the 300-330 mOsm/l media (P = 0.2372). Similar data were obtained for the VP neurons in PVN-derived cultures, but the OT neurons in these cultures survived significantly better at 300 mOs/l than at 255 mOsm/l (P<0.0001), but were not significantly different at 330 mOsm/l (P = 0.1208). In general, the VP neurons were more vulnerable than OT neurons to increases of culture medium osmolarity with respect to their survival. The number of OT/VP coexpressing neurons was greater in SON-derived cell cultures as compared to PVN-derived cell cultures, and their numbers were higher in the lower osmolarity media. The effects of adding brain-derived neurotrophic factor (BDNF) to the culture medium on survival were determined. BDNF significantly increased the numbers of all three types of neurons in both PVN and SON cell cultures (P = 0.0001-0.0060). The phenotypically identified cells, cultured in the 300 mOsm/l medium, responded by depolarization or hyperpolarization when transferred to hypertonic or hypotonic perfusion salines, respectively.

Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat

Cellular relationships between neurons producing vasopressin or vasoactive intestinal peptide in the suprachiasmatic nucleus of the hypothalamus, the main component of the central circadian timing system in mammals, were investigated in the rat using double immunocytochemistry. Analysis of serial confocal images revealed that the vasopressin-synthesizing neurons not only are important targets for the vasoactive intestinal peptide-synthesizing neurons, as previously demonstrated, but also establish reciprocal axosomatic contacts with these neurons, which have never been reported. On average, 5.4 vasoactive intestinal peptide contacts per vasopressin perikaryon and 1.7 vasopressin contacts per vasoactive intestinal peptide perikaryon were counted. That both types of neurons are linked by reciprocal synapses was confirmed at the electron microscopic level using a combination of immunoperoxidase and immunogold–silver labeling. Existence of an anatomical substrate for a vasopressinergic control of the vasoactive intestinal peptide neurons may have important functional consequences. In view (i) of the presumed, direct or indirect, involvement of the vasopressin neurons in relaying pacemaker information within and outside the suprachiasmatic nucleus, and (2) of the established role of the vasoactive intestinal peptide neurons as the main light-sensitive cells, it provides support for a neuronal mechanism through which the circadian clock may regulate inputs related to environmental messages. Our electron-microscopic data also extended earlier observations, pointing to the involvement of vasopressin and vasoactive intestinal peptide terminals in so-called double synapses that, conceivably, could regulate neuronal synchronization in the suprachiasmatic nucleus. A morphological basis for non-synaptic interactions that could be involved in ephaptic and/or paracrine communication between both types of peptidergic neurons is also reported.

Chapter 2.1.3 Phenotypic and state-dependent expression of the electrical and morphological properties of oxytocin and vasopressin neurones

Oxytocin and vasopressin secreting neurones of the hypothalamic supraoptic nucleus share many membrane characteristics and a roughly similar morphology. However, these two neurone types differ in the relative expression of some intrinsic and synaptic currents, and in the extent of their respective dendritic arbors. Spike depolarizing afterpotentials are present in both types, but more frequently give rise to prolonged burst discharges in vasopressin neurones. Oxytocin, but not vasopressin neurones, are characterized by a depolarization-activated, sustained outward rectifier which turns on near spike threshold, and which can produce prolonged spike frequency adaptation. When this sustained current is deactivated by small hyperpolarizing pulses, a rebound depolarization sufficient to evoke short spike trains follows the offset of these pulses. Both oxytocin and vasopressin neurones exhibit a transient outward rectification underlain by an Ia-type current. This transient rectifier delays spiking to depolarizing stimuli from a relatively hyperpolarized baseline, and is more prominent in vasopressin neurones. As a result, oxytocin neurones may be more reactive to depolarizing inputs. Both cell types receive glutamatergic, excitatory synaptic inputs and both possess R,S- alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subtypes. The AMPA receptor channel on both cell types is characterized by a relatively high calcium permeability and voltage-dependent rectification, characteristic of a diminished presence of the GluR2 AMPA subunit. However, AMPA-mediated synaptic transients are larger, and decay faster, in oxytocin compared with vasopressin neurones, suggesting a potential difference for synaptic integration. The characteristics of NMDA-mediated synaptic transients are similar in oxytocin and vasopressin neurones, but some data suggest NMDA receptors may be less involved in the glutamatergic activation of oxytocin neurones. In both cell types, synaptic release of glutamate often coactivates AMPA and NMDA receptors. The dendritic morphology of oxytocin and vasopressin neurones in female rats differs from one another and exhibits considerable plasticity as a function of endocrine state. In virgin rats, oxytocin neurones have more dendritic branches and a greater total dendritic length compared with lactation, when the arbor is much less extensive. A complementary change occurs in vasopressin dendrites, which are more extensive during lactation. This reorganization suggests that oxytocin neurones may be more electronically compact during lactation. In addition, such dramatic shifts in overall dendritic length imply that significant gains and losses in either the total number of synapses, or in synaptic density, are incurred by both cell types as a function of reproductive state.

Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.

Chapter 2.1.2 Neurophysiology of magnocellular neuroendocrine cells: Recent advances

Magnocellular neuroendocrine cells of the hypothalamic paraventricular and supraoptic nuclei are responsible for most of the vasopressin and oxytocin in the peripheral blood as well as for central release of these peptides in selected brain areas. As the principal component of the hypothalamo-neurohypophysial system, these neurons have been a subject of continual study for half a century. The wealth of solid information from decades of in vivo studies has provided a firm basis for in vitro, brain slice and explant investigations of neural mechanisms involved in the control and regulation of vasopressin and oxytocin neurons. In vitro methods have revealed the presence and permitted the study of monosynaptic projections to supraoptic neurons from the olfactory bulbs, the tuberomammillary nuclei of the posterior hypothalamus and from the organum vasculosum of the lamina terminalis. Such methods have also facilitated the elucidation of the various ionic currents controlling neurosecretory cell activity as well as the roles of calcium binding proteins and release of calcium from internal stores. This review summarizes recent advances in our understanding of the afferent inputs that impinge upon these two cell types, and the cellular and molecular mechanisms intrinsic to these neurons that determine their activity patterns and, in part, their responses to incoming stimuli.

Activation and degeneration during aging: a morphometric study of the human hypothalamus.

During the course of aging both activation and degenerative changes are found in the human hypothalamus. Degeneration may start around middle-age in some neurotransmitter- or neuromodulator-containing neurons. For instance, a decreased number of vasoactive intestinal polypeptide (VIP) neurons was observed in the suprachiasmatic nucleus (SCN) of middle-aged males. The normal circadian fluctuations seen in the number of vasopressin (AVP) neurons in the SCN of young subjects diminished in subjects older than 50 years. Moreover, a sharp decline in cell number was found in the sexually dimorphic nucleus (SDN) after 50 years in males. On the other hand, many hypothalamic systems remain perfectly intact during aging like the oxytocin (OXT) neurons in the paraventricular nucleus (PVN). The AVP neurons in the PVN are activated during aging as appears from their increasing cell number. Also the corticotrophin-releasing hormone (CRH) neurons of the PVN are activated in the course of aging, as indicated by their increased number and their increased AVP coexpression. Part of the infundibular nucleus, the subventricular nucleus, contains hypertrophic neurokinin B neurons in postmenopausal women. It can be concluded that a multitude of changes in the various hypothalamic nuclei may be the biological basis for many functional changes in aging, i.e., both endocrine and central alterations, and that only a minority of the possible human hypothalamic changes have so far been studied.

Drinking and Fos-immunoreactivity in rat brain induced by local injection of angiotensin I into the subfornical organ

Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiotensin I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and paraventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT1 receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.

Chapter 2.1.1 Osmoregulation of vasopressin neurons: A synergy of intrinsic and synaptic processes

The release of vasopressin into the general circulation varies as a function of plasma osmolality and therefore plays a major role in systemic osmoregulation. In vivo, the secretion of this hormone in the neurohypophysis is primarily determined by the rate of action potential discharge of the magnocellular neurosecretory cells (MNCs) in the hypothalamus. Experiments done over the past 20 years have clarified much of the neurophysiological basis underlying this important osmoregulatory reflex. As discussed here, recent findings indicate that the regulation of the firing rate of MNCs during changes in systemic osmolality involves the concerted modulation of mechanosensitive ion channels in MNCs, as well as excitatory glutamatergic inputs derived from forebrain regions such as the organum vasculosum of the lamina terminalis.

Noradrenergic Excitation of Magnocellular Neurons in the Rat Hypothalamic Paraventricular Nucleus via Intranuclear Glutamatergic Circuits

Noradrenergic projections to the hypothalamus play a critical role in the afferent control of oxytocin and vasopressin release. Recent evidence for intrahypothalamic glutamatergic circuits prompted us to test the hypothesis that the excitatory effect of noradrenergic inputs on oxytocin and vasopressin release is mediated in part by local glutamatergic interneurons. The voltage response to norepinephrine (30-300 microM) was tested with whole-cell recordings in putative magnocellular neurons of the paraventricular nucleus (PVN) in hypothalamic slices (400 micrometers). Norepinephrine elicited an alpha1 receptor-mediated direct depolarization in 23% of the magnocellular neurons tested; however, the most prominent response, seen in 42% of the magnocellular neurons, was an alpha1 receptor-mediated increase in the frequency of EPSPs. The norepinephrine-induced increase in EPSPs was blocked by tetrodotoxin and by ionotropic glutamate receptor antagonists, suggesting that norepinephrine excited presynaptic glutamate neurons to cause an increase in spike-mediated transmitter release. The increase in EPSPs also was observed in a surgically isolated PVN preparation (64% of cells) and with microdrop applications of norepinephrine (1 mM, 33% of cells) and glutamate (0.5-1 mM, 28%) in the PVN, indicating that the norepinephrine-sensitive presynaptic glutamate neurons are located within the PVN. Biocytin injection and subsequent immunohistochemical labeling revealed that both oxytocin and vasopressin neurons responded to norepinephrine. Our data indicate that magnocellular neurons of the PVN receive excitatory inputs from intranuclear glutamatergic neurons that express alpha1-adrenoreceptors. These glutamatergic interneurons may serve as an excitatory relay in the afferent noradrenergic control of oxytocin and vasopressin release under certain physiological conditions.

Afferent renal inputs to paraventricular nucleus vasopressin and oxytocin neurosecretory neurons

Extracellular single-unit recording experiments were done in pentobarbital sodium-anesthetized rats to investigate the effects of electrical stimulation of afferent renal nerves (ARN) and renal vein (RVO) or artery (RAO) occlusion on the discharge rate of putative arginine vasopressin (AVP) and oxytocin (Oxy) neurons in the paraventricular nucleus of the hypothalamus (PVH). PVH neurons antidromically activated by electrical stimulation of the neurohypophysis were classified as either AVP or Oxy secreting on the basis of their spontaneous discharge patterns and response to activation of arterial baroreceptors. Ninety-eight putative neurosecretory neurons in the PVH were tested for their response to electrical stimulation of ARN: 44 were classified as putative AVP and 54 as putative Oxy neurons. Of the 44 AVP neurons, 52% were excited, 7% were inhibited, and 41% were nonresponsive to ARN stimulation. Of the 54 Oxy neurons, 43% were excited, 6% inhibited, and 51% were not affected by ARN. An additional 45 neurosecretory neurons (29 AVP and 16 Oxy neurons) were tested for their responses to RVO and/or RAO. RVO inhibited 42% of the putative AVP neurons and 13% of the putative Oxy neurons. On the other hand, RAO excited 33% of the AVP and 9% of the Oxy neurons. No AVP or Oxy neurons were found to be excited by RVO or inhibited by RAO. These data indicate that sensory information originating in renal receptors alters the activity of AVP and Oxy neurons in the PVH and suggest that these renal receptors contribute to the hypothalamic control of AVP and Oxy release into the circulation.

Metabotropic glutamate receptor in vasopressin, CRF and VIP hypothalamic neurones

The excitatory amino acid glutamate, acting via ionotropic and metabotropic glutamate receptors, appears to play an important role in the control of neuroendocrine functions. The aim of the present investigations was to determine whether hypothalamic neurones which synthesize arginin-vasopressin (AVP), CRF and VIP express metabotropic glutamate receptor (mGluR). Double-label immunocytochemistry and the mirror technique were used. We found that AVP immunoreactive neurones of the paraventricular, supraoptic and suprachiasmatic nuclei contain mGluR1a, but the number of double-labelled neurones was different in the three cell groups. mGluR1a was present in a significant number of paraventricular CRF nerve cells, and in almost all VIP neurones of the SCHN. These results support the view that the excitatory transmitter glutamate may directly influence AVP, CRF and VIP neurones of the three hypothalamic cell groups.

Comparison of the expression of two immediate early gene proteins, FosB and Fos in the rat preoptic area, hypothalamus and brainstem during pregnancy, parturition and lactation

Medial preoptic area (MPA), supraoptic nucleus (SON), magnocellular (MaPVN) and parvocellular (PaPVN) paraventricular hypothalamic nuclei, and mesencephalic lateral tegmentum (MLT) are involved in maternal behavior, parturition and lactation. This study investigated the FosB and Fos immunoreactivity in these regions of virgin, pregnant, parturient, lactating, and lactating-arrested rats. The patterns of FosB and Fos expression were compared between the sections taken from the same animals. Quantitative immunohistochemistry revealed a significant increase in the numbers of FosB-positive neurons in the MPA, SON, MaPVN, and MLT of parturient and lactating females as compared with pregnant or virgin animals. In lactating rats, the numbers of FosB-positive neurons in the MPA, PaPVN, and MLT were increased, but the numbers in the SON and MaPVN were decreased as compared with parturient females. Many Fos-positive neurons were also seen in parturient and lactating rats, and the patterns of Fos expression in each region were quite similar to those of FosB. Moreover, double-labeling immunohistochemistry revealed that: (1) many FosB-positive nuclei were observed in oxytocin and vasopressin neurons of the SON and PVN in parturient rats; (2) within FosB-positive neurons, 89.5% in the MPA, 86.8% in the MLT of parturient rats, and 92% in the MPA and 90.8% in the MLT of lactating animals were also Fos-positive. Only a small number of FosB and Fos-positive neurons were seen in females that were killed in the early stage of parturition. Removal of the litters immediately after parturition completely eliminated FosB and Fos expression in each region in the dams. Taken together, the present results suggest that FosB expression is co-involved with Fos in the neural activation during parturition and lactation in rats.

Stability analysis of the FitzHugh-Nagumo differential equations driven by impulses: applied to the electrical firing of magnocellular neurons

A stability analysis is carried out for a mathematical model which describes the electrical firing of a single vasopressin neuron. The model used in a FitzHugh-Nagumo-type system which is driven by impulses. The analysis is based on recent developments in the stability theory of impulsive differential equations. Conditions are derived under which the system of differential equations is stable at two of its equilibrium points. Biologically this bistability represents the cell alternating between periods of electrical activity and silence. The conditions for stability are specified in terms of the amplitude and frequency of the impulses perturbing the system. Both stochastic and deterministic impulses are considered.