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L P Renaud

Publications and source records attributed to L P Renaud.

At least 19 recordsLinked to original sources
PubMed1995

Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurones in vivo by glutamate receptors.

1. Vasopressin-secreting neurones in the rat hypothalamic supraoptic nucleus display patterned spontaneous phasic activity, which is apparently maintained in vivo through yet unidentified neurotransmitter system(s). The present investigation used extracellular recording techniques in anaesthetized Long-Evans rats to evaluate whether the neurotransmitter mechanism underlying phasic firing is provided via a family of ionotropic glutamate receptors. 2. N-Methyl-D-aspartate (NMDA) reliably evoked bursts of activity in twenty-seven of twenty-eight phasic neurones. Amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainate also elicited pronounced excitations in twenty-one of twenty-one and and fourteen of fifteen phasic cells, respectively. 3. A rapid blockade of on-going phasic activity was consistently induced following brief applications of both NMDA and non-NMDA receptor antagonists; extended application of antagonists resulted in prolonged silent periods, during which phasic activity failed to recur for minutes. Neither saline nor a cholecystokinin receptor antagonist influenced cell firing. 4. In contrast to putative vasopressin cells, application of NMDA receptor ligands did not affect the spontaneous activity in most putative oxytocin-secreting neurones, whereas kainate and AMPA potently excited seven of nine and four of five putative oxytocin cells, respectively. 5. These results imply that the maintenance of spontaneous phasic discharges in vivo in supraoptic vasopressin-secreting neurones requires tonic synaptic activation involving both NMDA and non-NMDA glutamate receptors. In putative oxytocin-secreting neurones, spontaneous firing appears to be predominantly regulated by non-NMDA receptors. Glutamatergic innervations may be in a unique position to influence the genesis of patterned electrical activity in supraoptic vasopressin neurones.

2-Amino-5-phosphonovalerate↗
PubMed1995

Cholecystokinin evokes vasopressin release from perfused hypothalamic-neurohypophyseal explants.

Cholecystokinin (CCK) may have a transmitter/modulator role in the hypothalamic magnocellular neurosecretory system. In the rat, the supraoptic and paraventricular nuclei display high affinity binding for radiolabelled CCK. Exogenously applied CCK depolarizes supraoptic neurons, acting at postsynaptic CCK-B type receptors. The present study evaluated the ability for the sulfated octapeptide of CCK (CCK-8S), which is a predominate form of this peptide in brain, to evoke release of vasopressin from the neurohypophysis of intra-arterially perfused hypothalamic explants. 3 min applications of 1 microM CCK-8S through the intra-arterial perfusion medium prompted an elevation of vasopressin in samples taken from the neurointermediate lobe in 10 of 14 preparations. Vasopressin levels rose from undetectable baseline values to a peak of 29.5 +/- 6.7 pg/ml (mean +/- S.E.M). This response was dose-dependent and was abolished by pituitary stalk transection (5/5 explants). Locally applied CCK-8S (25-200 pmol) through bilateral infusions onto the ventral surface of the supraoptic nucleus also induced a dose-dependent release of vasopressin (5/7 explants). These observations suggest that CCK can act at receptors located on (or near) the somata of supraoptic nucleus neurons to induce neuronal discharges that are conducted to the neural lobe where they evoke release of vasopressin from neurohypophysial axon terminals.

Animals↗
PubMed1994

GABA receptor mediation of median preoptic nucleus-evoked inhibition of supraoptic neurosecretory neurones in rat.

1. This study evaluated the influence of focal electrical and chemical microstimulation in the median preoptic nucleus (MnPO) on the excitability of putative vasopressin and oxytocin neurones recorded in the supraoptic nucleus of urethane- or pentobarbitone-anaesthetized rats. 2. In vasopressin neurones, single 1 Hz stimulation reduced the excitability of 120/139 cells. Trains of repetitive 5-30 Hz stimulation, or microinfusion of glutamate into the MnPO, similarly induced a cessation in spontaneous phasic or continuous firing in 17/18 and 17/20 vasopressin neurones, respectively. In 20/21 cells, locally applied bicuculline (100 microM) attenuated MnPO-evoked depressant responses whereas strychnine (100 microM) and timolol (20 microM) were without effect on 5/5 vasopressin neurones. In three cells, bicuculline applications were associated with marked increases in MnPO-evoked excitations. 3. In oxytocin neurones, single-pulse (1 Hz) electrical stimulation in MnPO evoked an increase in the excitability in 51/59 cells. However, in 6/7 oxytocin cells tested, glutamate microinfusions into MnPO induced prolonged suppression in firing. During trains of stimuli (5-30 Hz), 26/44 cells displayed an initial increase in firing associated with the first few impulses but this was then replaced by suppression of activity; another ten cells displayed excitation alone, and eight cells demonstrated only suppression. The depressant responses evoked during trains of MnPO stimulation were blocked by 100 microM bicuculline (6/6 cells tested) whereas strychnine was ineffective (2/2 cells tested). 4. These results suggest that the MnPO provides a mainly depressant influence on supraoptic vasopressin and oxytocin neurones, perhaps through the activation of postsynaptic GABAA receptors.

Animals↗
PubMed1994

Overexpression of activin-beta A subunit mRNA is associated with decreased activin type II receptor mRNA levels in the testes of alpha-inhibin deficient mice.

Activins and inhibins are polypeptides of the transforming growth factor-beta family that participate in differentiation and growth of diverse cell types, and are involved in endocrine/paracrine regulation of the hypothalamo-pituitary-gonadal axis. Mice with alpha-inhibin subunit gene deletion develop large testicular tumors. In these animals, a 200-fold increase in testicular expression of activin beta A subunit mRNA was detected using S1-nuclease protection analysis. Northern blot analysis demonstrated that a predominant mRNA form of approximately 6.5 kb and a second minor form of 4.5 kb were overexpressed in the testes of the alpha-inhibin deficient animals. Testicular expression of the type II activin receptor was decreased 3-fold in these mice. In contrast, hypothalamic beta A and type II activin receptor mRNA levels remained unaltered. alpha-Inhibin may play a role to suppress the expression of beta A mRNA in the mammalian testes. These results demonstrate that increased expression of activin is accompanied by a tissue specific reduction in the expression of its own receptor mRNA in vivo.

Activin Receptors↗
PubMed1994

Organum vasculosum lamina terminalis-evoked postsynaptic responses in rat supraoptic neurones in vitro.

1. To characterize the organum vasculosum lamina terminalis (OVLT) innervation of hypothalamic supraoptic nucleus (SON) neurones, current clamp recordings were obtained in SON cells in superfused rat hypothalamic explants. Stimulation of 1 Hz evoked 5-10 mV bicuculline-sensitive IPSPs in forty out of forty-six SON neurones, including both phasic (vasopressin immunoreactive) and continuously firing (oxytocin immunoreactive) cells. 2. In twenty-four cells, mean IPSP latency was 8.7 +/- 1 ms (+/- S.D.) and reversal potentials (Vr) ranged between -60 and -75 mV. In the other sixteen cells, Vr ranged between -20 and -55 mV and the addition of bicuculline revealed underlying EPSPs (latency, 7.8 +/- 0.8 ms; mean Vr, -8 +/- 10 mV) with two components: (a) fast (rise and half-decay times of 5.83 +/- 1.3 ms and 19 +/- 4.4 ms respectively), with reversible blockade by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); (b) slow (4- to 5-fold increase in rise and half-decay time), with reversible reduction by (-)-aminophosphonovaleric acid (APV). 3. During 10 Hz stimulation, EPSPs summated into 3-7 mV depolarizing envelopes lasting 1.5-3.0 s and sustaining action potential bursts. Depolarizing envelopes displayed voltage dependence, and were enhanced after removal of extracellular magnesium, diminished by APV and completely abolished by APV and CNQX together. 4. Thus, non-NMDA receptors probably mediate fast EPSPs whereas NMDA receptors mediate slow EPSPs and depolarizing envelopes. OVLT-evoked EPSPs were only seen in vasopressin-immunoreactive neurones. 5. These observations indicate converging inhibitory and target-selective excitatory amino acid-mediated inputs from OVLT to SON; the latter may modulate the excitability of SON vasopressin neurones to a hyperosmotic challenge.

2-Amino-5-phosphonovalerate↗
PubMed1994

Ultrastructural evidence for intra- and extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus.

GABAergic projections of the suprachiasmatic nucleus (SCN) were demonstrated in a double-labelling ultrastructural study which visualised the efferents of the SCN by PHA-L tracing, diaminobenzidine (DAB) immunocytochemistry, and GABA with immunogold postembedding staining. The results show a strong contralateral projection of the SCN that is partly GABA-containing. In addition, ipsilateral SCN projections to the dorsomedial hypothalamus and periventricular part of the paraventricular nucleus and sub-paraventricular nucleus were shown to contain GABA. The present results indicate that the SCN may utilize this inhibitory neurotransmitter to regulate and organize its own circadian rhythm as well as using GABA to transmit its diurnal information to other regions of the brain.

3,3'-Diaminobenzidine↗
PubMed1994

N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo.

Supraoptic neurosecretory neurons express a prominent N-methyl-D-aspartate receptor system. Recent in vitro evidence reveals that N-methyl-D-aspartate receptor activation dramatically alters the spontaneous discharge patterns of supraoptic neurons. In this study we evaluate whether N-methyl-D-aspartate receptors in vivo contribute to the development of characteristic phasic discharge patterns displayed by vasopressin-secreting neurons. Intravenous administration of ketamine hydrochloride, a non-competitive N-methyl-D-aspartate receptor antagonist, was used to examine whether N-methyl-D-aspartate receptor blockade influences patterned spontaneous discharge observed in supraoptic neurosecretory neurons. Extracellular recordings were obtained from identified hypothalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats. Systemic administration of ketamine (< or = 1.5 mg/kg) potently suppressed spontaneous phasic discharge in 16/19 putative vasopressin-secreting cells. The ketamine-induced blockade was dose dependent, fully reversible and was associated with the complete blockade of activity evoked by local pressure application of N-methyl-D-aspartate, but not the activity evoked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no detectable effect on threshold or shape of antidromic action potentials. By comparison, the activity in 9/10 continuously active neurons (putative oxytocin-secreting) was unaffected by administration of identical doses of ketamine. These data suggest that N-methyl-D-aspartate receptors play an important role in regulating the onset and maintenance of spontaneous phasic activity patterns displayed by rat supraoptic vasopressin neurons in vivo.

Animals↗
PubMed1994

Perinuclear zone and diagonal band lesions enhance angiotensin responses of rat supraoptic neurons.

Sinoaortic denervation in the rat is associated with an increased sensitivity of vasopressin neurons in the supraoptic nucleus (SON) to peripheral angiotensin II (ANG II). Lesion studies have indicated that the diagonal band of Broca (DBB) and the perinuclear zone of the SON in the lateral hypothalamus (PNZ) are essential components in the central pathway for the baroreceptor inhibition of vasopressin SON neurons. The present study examined the effect of ibotenate lesions in either the DBB or the lateral hypothalamus, which includes the PNZ, on the responses of SON neurons to peripherally administered ANG II (500 pmol/kg ia). Extracellular recordings obtained from vasopressin SON neurons in pentobarbital-anesthetized rats indicate that DBB and PNZ lesions not only interrupted the baroreceptor-mediated inhibition of SON neurons but also significantly increased the excitatory effects of ANG II on putative vasopressin SON neurons. These results suggest that ibotenate lesions of the DBB and the lateral hypothalamus that include the PNZ affect the ANG II-induced activation of putative vasopressin SON neurons in a manner consistent with results obtained from baroreceptor-denervated rats.

Angiotensin II↗
PubMed1993

Norepinephrine injections in diagonal band of Broca selectively reduced the activity of vasopressin supraoptic neurons in the rat.

In the rat, transient drug-induced elevations of arterial blood pressure, which are sufficient to activate peripheral baroreceptors, produce a brief and selective cessation in the spontaneous activity of vasopressin-secreting cells in the hypothalamic supraoptic nucleus. This response appears to require the noradrenergic innervation of the diagonal band of Broca. The present study evaluated whether injections of norepinephrine into the diagonal band of Broca affect the spontaneous activity of supraoptic vasopressin-secreting neurons. Extracellular recordings were obtained from antidromically identified supraoptic neurons in pentobarbital anesthetized rats using a transpharyngeal approach. Injections of 200 nl of 10 microM norepinephrine into the diagonal band of Broca region arrested the spontaneous activity of 80% (12/15) of vasopressin-secreting neurons but only 7% (1/14) of oxytocin secreting-neurons demonstrated a comparable decrease in excitability. Vehicle injections did not influence the activity of any of the neurons tested. These results are consistent with the hypothesis that the baroreceptor-sensitivity of vasopressin neurons is mediated by a noradrenergic mechanism in the diagonal band of Broca.

Action Potentials↗
PubMed1993

Differential responses of identified rat hypothalamic paraventricular neurons to suprachiasmatic nucleus stimulation.

The suprachiasmatic nucleus in the anterior hypothalamus contains a circadian oscillator that is responsible for 24-h rhythms in several behavioral, endocrine and autonomic processes. Efferent suprachiasmatic projections are likely to transmit rhythmic information to brain nuclei controlling these functions. The hypothalamic paraventricular nucleus is considered to be a target of the suprachiasmatic nucleus due to its important role in autonomic and endocrine regulation. The present study applied extracellular electrophysiological techniques to intact animals to look for a possible interaction between suprachiasmatic nucleus efferents and identified neurons in the hypothalamic paraventricular nucleus. Results showed that electrical stimulation of the suprachiasmatic nucleus induced an increase in the excitability of 87% of paraventricular neurons that project to the median eminence and are situated in the medial and dorsal parvocellular subnucleus; neurons with similar projections but located in the periventricular subnucleus displayed a reduction in firing rate following suprachiasmatic stimulation. Electrical activation of the suprachiasmatic nucleus provoked a decrease in excitability in 75% of paraventricular neurons in the posterior magnocellular subnucleus that send axons to the posterior pituitary and in 85% of paraventricular neurons, located in the medial parvocellular subnucleus, that project to the dorsal vagus complex in the brainstem. The data imply that functional and selective neural connections exist between suprachiasmatic nucleus efferents and specific cell groups within the hypothalamic paraventricular nucleus. These projections would be able to convey rhythmic information to certain endocrine and autonomic functions. The anatomical and neurochemical characteristics of the underlying pathways remain to be determined.

Afferent Pathways↗
PubMed1993

Depolarizing action of secretory granule protein 7B2 on rat supraoptic neurosecretory neurons.

A novel precursor neuropeptide termed 7B2 is present within specific brain areas, including the hypothalamic magnocellular neurosecretory neurons, and appears to be processed to smaller fragments. In order to determine whether specific C-terminal fragments of 7B2 might exert local effects on neurosecretory cells, we used intracellular current-clamp recordings in supraoptic neurons maintained in superfused hypothalamic explants to evaluate membrane potential and resistance changes in 25 supraoptic nucleus neurons during bolus applications of 7B2 174-186 and two other C-terminal peptide fragments 7B2 156-173 and 7B2 141-150. In 15 supraoptic neurons, only the 7B2 174-186 fragment induced a gradual 2-8 mV membrane depolarization that lasted for 4 to 30 min and was accompanied by 15+/-8% reduction in input resistance. Immunocytochemical identification of the recorded cells revealed that both vasopressin (VP)- and oxytocin (OT)-containing neurons were depolarized by 7B2 174-186. These data suggest that 7B2 174-186 is a biologically active fragment of 7B2 and may regulate the excitability of magnocellular supraoptic nucleus neurons.

Animals↗
PubMed1993

Lateral hypothalamic lesions alter baroreceptor-evoked inhibition of rat supraoptic vasopressin neurones.

1. Previous electrophysiological studies on rat hypothalamic supraoptic nucleus neurones have demonstrated that both the activation of peripheral baroreceptors (induced by a brief rise in arterial pressure consequent to an intravenous injection of an alpha-adrenergic agonist, metaraminol) and electrical stimulation in the diagonal band of Broca evokes a GABA-mediated postsynaptic inhibition which selectively involves the phasic-firing (putative vasopressin-secreting) neuronal population. Although baroreceptor-triggered inhibitions are abolished after diagonal band lesions, anatomical data support the hypothesis that the GABAergic neurones mediating both the baroreflex and electrically induced inhibitions are not located in the diagonal band, but rather in the lateral hypothalamus adjacent to the supraoptic nucleus. To determine the validity of this hypothesis, excitotoxic lesions were placed in the lateral hypothalamus and their effects on both baroreceptor- and diagonal band-evoked inhibitions were evaluated. 2. Male Long-Evans rats were initially anaesthetized with intraperitoneal pentobarbitone, stereotaxically injected with an excitotoxin (ibotenic acid) or vehicle into the lateral hypothalamus on the left side and allowed to recover. Three or more days later, animals were again anaesthetized with pentobarbitone and the ventral surface of their hypothalamus was exposed for electrophysiological recording of neurones in the left supraoptic nucleus. In all injected animals, extracellular recordings from antidromically identified, phasically firing supraoptic neurones were evaluated for their response to activation of peripheral baroreceptors and to electrical stimulation in the diagonal band. 3. Increases in arterial pressure sufficient to activate peripheral baroreceptors were achieved by intravenous bolus infusions of metaraminol (10 micrograms/10 microliters). In vehicle control animals (n = 6), the activity of 34/39 neurones was inhibited by baroreceptor activation. In lesion control animals (n = 13) similar inhibitions were observed from 60/65 neurones. In the lateral hypothalamic lesioned group (n = 7), the activity of only 12/34 neurones were inhibited by similar elevations in blood pressure. 4. Ibotenic acid lesions in the lateral hypothalamus also disrupted the responsiveness of supraoptic neurones to electrical stimulation in the diagonal band. Whereas diagonal band stimulation in vehicle control and lesion control rats reduced the excitability in 7/9 cells and 15/19 cells respectively, only 1/7 cells responded in the lesioned animals. 5. Lesions having a significant effect on the responsiveness of vasopressin-secreting neurones to baroreceptor activation extended laterally towards the nucleus of the lateral olfactory tract, dorsally into the striatum and medially to the fornix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Membrane properties of organum vasculosum lamina terminalis neurons recorded in vitro.

Intracellular recordings of organum vasculosum lamina terminalis (OVLT) neurons were obtained from superfused explants of rat hypothalamus. Most (32 of 34) OVLT neurons displayed a low threshold spike response during depolarizing pulses applied from holding membrane potentials negative to -70 mV. In 17 of 34 cells, electrical stimulation of the supraoptic nucleus area evoked antidromic responses. In 20 of the 34 cells, 8 of which were antidromically driven, identical stimuli also revealed either excitatory (n = 12) or inhibitory (n = 5) or mixed (n = 3) postsynaptic potentials. Axonal projections to the ipsilateral supraoptic nucleus were confirmed afterwards using reconstruction of Lucifer yellow-filled cells. A 10-40 mosmol/kgH2O increase in the osmolality of the superfusion media by addition of NaCl or mannitol prompted a membrane depolarization of 2-10 mV in each of nine OVLT neurons tested. These results indicate that OVLT neurons project to the supraoptic nucleus and possess intrinsic properties capable of influencing their excitability. Because neurons in OVLT depolarize consequent to elevations in media osmolality, the OVLT may provide a means by which hyperosmotic stimuli influence neuroendocrine function.

Animals↗
PubMed1992

Rat supraoptic neurons are resistant to glutamate neurotoxicity.

Magnocellular neurosecretory cells of the supraoptic nucleus (SON) are thought to be endogenously resistant to glutamate toxicity. In this study, we sought physiological and morphological evidence of this resistance in rats that received multiple peri-nuclear injections of ibotenate. In this preparation, ibotenate produced a large necrotic zone encompassing the SON but not within the nucleus itself. Extracellular recordings in vivo from 68 'spared' SON neurons from lesioned rats revealed normal patterns of electrical activity. Intracellular analysis in vitro from 13 'spared' SON neurons indicated that their intrinsic membrane properties, osmosensitivity and spontaneous synaptic activity did not differ significantly from that of controls. We conclude that SON neurons retain both a morphological and a physiological resistance to glutamate neurotoxicity.

Animals↗
PubMed1992

Depolarizing action of cholecystokinin on rat supraoptic neurones in vitro.

1. Cholecystokinin is co-localized within the oxytocin- and, to a lesser extent, vasopressin-synthesizing magnocellular neurones in the hypothalamic supraoptic and paraventricular nuclei. These nuclei are also prominent binding sites for cholecystokinin. In the present study we used intracellular current- and voltage-clamp recordings from fifty-seven supraoptic nucleus cells, maintained in superfused explants of rat hypothalamus, to assess their membrane responses to exogenous cholecystokinin and define the nature of their cholecystokinin receptors. 2. In a majority of the fifty-seven cells tested, bolus infusions into the superfusion media of cholecystokinin fragments (maximum concentrations estimated at 0.3-15 microM) were followed within 1-5 s by a transient and reversible membrane depolarization. Active peptides included sulphated cholecystokinin octapeptide (26-33) (28 of 33 cells responded), non-sulphated cholecystokinin octapeptide (26-33) (21 of 25 cells responded), cholecystokinin tetrapeptide (30-33) (20 of 24 cells responded and caerulein (4 of 4 cells responded). None of five cells responded to cholecystokinin (26-28). Depolarizing responses to cholecystokinin analogues persisted in the presence of tetrodotoxin (0.2-0.4 microM), and in Ca(2+)-free solutions containing MnCl2 (2.5 mM). 3. Under voltage clamp, cholecystokinin fragments evoked an inward current accompanied by an increase in membrane conductance. The amplitude of the inward current varied linearly as a function of membrane voltage, with an extrapolated reversal potential of approximately -15 mV. Reversal potentials were not altered by chloride injection. These features suggest that cholecystokinin activates a non-selective cationic conductance. 4. Active cholecystokinin analogues were approximately equipotent in their depolarizing actions, a feature that supports the activation of cholecystokinin-B type receptors. Moreover bath application of 200 nM L-365,260, an antagonist with a high affinity for cholecystokinin-B receptors, reversibly attenuated the cholecystokinin-induced responses in four of six cells tested. 5. These observations indicate that cholecystokinin can directly influence the excitability of rat supraoptic nucleus neurones and provide evidence for an additional site where this peptide may act within the hypothalamo-neurohypophysial axis.

Action Potentials↗