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Brian J. Oldfield - One of the best experts on this subject based on the ideXlab platform.
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the trajectory of sensory pathways from the Lamina Terminalis to the insular and cingulate cortex a neuroanatomical framework for the generation of thirst
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2008Co-Authors: Jacob Harvey Hollis, M J Mckinley, Moyra Dsouza, Juliane Kampe, Brian J. OldfieldAbstract:The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex. After 2 days of infection, pseudorabies-positive neurons were identified within the thalamus and Lamina Terminalis. In a separate group of rats, the retrograde tracer cholera toxin subunit b (CTb) was used in combination with either isotonic (0.15 M NaCl) or hypertonic (0.8 M NaCl) saline (1 ml/100 g body wt ip). Rats injected with CTb in the insular cortex and stimulated with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the paraventricular, rhomboid, and reuniens thalamic nuclei, whereas those rats injected with CTb in the cingulate cortex and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the medial part of the mediodorsal, interanteromedial, anteromedial, and ventrolateral part of the laterodorsal thalamic nuclei. Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the Lamina Terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ. A small proportion of the CTb-positive neurons in the OVLT were immunopositive for transient receptor potential vanilloid 1, a putative osmoresponsive membrane protein. These results identify functional thalamocortical pathways involved in relaying osmotic signals to the insular and cingulate cortex and may provide a neuroanatomical framework for the emotional aspects of thirst.
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vasopressin secretion osmotic and hormonal regulation by the Lamina Terminalis
Journal of Neuroendocrinology, 2004Co-Authors: M J Mckinley, Robin M. Mcallen, Michael L Mathai, R C Mcclear, Richard R Miselis, G L Pennington, L Vivas, Johh D Wade, Brian J. OldfieldAbstract:The Lamina Terminalis, located in the anterior wall of the third ventricle, is comprised of the subfornical organ, median preoptic nucleus (MnPO) and organum vasculosum of the Lamina Terminalis (OVLT). The subfornical organ and OVLT are two of the brain's circumventricular organs that lack the blood–brain barrier, and are therefore exposed to the ionic and hormonal environment of the systemic circulation. Previous investigations in sheep and rats show that this region of the brain has a crucial role in osmoregulatory vasopressin secretion and thirst. The effects of lesions of the Lamina Terminalis, studies of immediate–early gene expression and electrophysiological data show that all three regions of the Lamina Terminalis are involved in osmoregulation. There is considerable evidence that physiological osmoreceptors subserving vasopressin release are located in the dorsal cap region of the OVLT and possibly also around the periphery of the subfornical organ and in the MnPO. The circulating peptide hormones angiotensin II and relaxin also have access to peptide specific receptors (AT1 and LGR7 receptors, respectively) in the subfornical organ and OVLT, and both angiotensin II and relaxin act on the subfornical organ to stimulate water drinking in the rat. Studies that combined neuroanatomical tracing and detection of c-fos expression in response to angiotensin II or relaxin suggest that both of these circulating peptides act on neurones within the dorsal cap of the OVLT and the periphery of the subfornical organ to stimulate vasopressin release.
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distribution of fos immunoreactivity in the Lamina Terminalis and hypothalamus induced by centrally administered relaxin in conscious rats
Journal of Neuroendocrinology, 2003Co-Authors: M J Mckinley, Brian J. Oldfield, R S Weisinger, Peta Burns, L M Colvill, John D Wade, Geoffrey W TregearAbstract:Abstract The effect of intracerebroventricular (ICV) injections of synthetic human or rat relaxin (25 or 250 ng) on the distribution of Fos detectedimmunohistochemically in the rat forebrain was investigated. Following ICV relaxin, many Fos-positive neurons were observed in theperiphery of the subfornical organ, dorsal part of the organum vasculosum of the Lamina Terminalis, throughout the median preopticnucleus, supraoptic nucleus and hypothalamic paraventricular nucleus. Such effects did not occur following ICV injection of artificialcerebrospinal fluid or the separated A and B chains of relaxin, nor following the intravenous injection of 250 ng of relaxin. Both vasopressinand oxytocin containing neurons identified immunohistochemically in the supraoptic and paraventricular nuclei exhibited Fos followingICV relaxin, and many neurons in the medial parvocellular part of the paraventricular nucleus contained Fos. The results indicate thatcentrally administered relaxin may increase neuronal activity in regions of the hypothalamus and Lamina Terminalis which are associatedwith cardiovascular and body fluid regulation and oxytocin secretion.Administration of the ovarian hormone relaxin into the brain In order to identify more of the neural substrates mediatinginduces a number of neuroendocrine, cardiovascular and behavi- the actions of centrally administered relaxin, we have studied theoural responses (1). For example, it was shown initially that distribution of Fos expression after ICV injection of relaxin inintracerebroventricular (ICV) injection ofporcine relaxin disrupts conscious male rats. Expression of the immediate early genethe milk-ejection reflex and oxytocin release in lactating rats (2, c-fos and subsequent production of its encoded protein Fos3, 4). ICV relaxin also stimulates vasopressin release (5), a is a consequence of neuronal activation (15, 16). Immuno-pressor response (5) and water drinking in rats (6, 7). The histochemical detection of Fos has provided a convenient meanssubfornical organ has been implicated in the central actions of of detecting increased activity of neurons throughout the CNS ofrelaxin because the pressor response and inhibition of the milk conscious animals subjected to specific stimuli (15, 16, 17).ejection reflex caused by ICV relaxin are prevented by ablationof this circumventricular organ (5, 8). However, conclusionsdrawn from such experiments are somewhat limited because
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Neural Pathways From The Lamina Terminalis Influencing Cardiovascular And Body Fluid Homeostasis
Clinical and experimental pharmacology & physiology, 2001Co-Authors: Michael J. Mckinley, Brian J. Oldfield, Andrew M. Allen, Clive N. May, Robin M. Mcallen, David J. Sly, Frederick A.o. MendelsohnAbstract:SUMMARY 1. The Lamina Terminalis, a region of the brain with a high concentration of angiotensin AT1 receptors, consists of three distinct nuclei, the median preoptic nucleus, the subfornical organ and organum vasculosum of the Lamina Terminalis (OVLT). These latter two regions lack a blood–brain and detect changes in plasma angiotensin (Ang) II concentration and osmolality. 2. Efferent neural pathways from the Lamina Terminalis to the hypothalamic paraventricular and supraoptic nuclei mediate vasopressin secretion in response to plasma hypertonicity and increased circulating levels of AngII. 3. Studies using the neurotropic virus pseudorabies, which undergoes retrograde transynaptic neuronal transport following injection into peripheral sites, show that neurons in the Lamina Terminalis have efferent polysynaptic neural connections to the peripheral sympathetic nervous system. Some of these neurons have been shown to have polysynaptic connections to the kidney and to express AT1 receptor mRNA. We propose that circulating AngII acts at AT1 receptors in the subfornical organ and OVLT to influence the sympathetic nervous system. It is likely that the neural pathway subserving this influence involves a synapse in the hypothalamic paraventricular nucleus. 4. The Lamina Terminalis may exert an inhibitory osmoregulatory influence on renin secretion by the kidney. This osmoregulatory influence may be mediated by inhibition of renal sympathetic nerve activity and appears to involve a central angiotensinergic synapse. 5. The Lamina Terminalis exerts an osmoregulatory influence on renal sodium excretion that is independent of the renal nerves and is probably hormonally mediated.
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activation of kidney directed neurons in the Lamina Terminalis by alterations in body fluid balance
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2001Co-Authors: David Sly, M J Mckinley, Brian J. OldfieldAbstract:This study was undertaken to determine if neurons in the Lamina Terminalis, previously identified as projecting to the kidney (35), were responsive to alterations in stimuli associated with fluid b...
M J Mckinley - One of the best experts on this subject based on the ideXlab platform.
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increased cardiac sympathetic nerve activity in ovine heart failure is reduced by lesion of the area postrema but not Lamina Terminalis
Basic Research in Cardiology, 2018Co-Authors: M J Mckinley, Yonis Abukar, Rohit Ramchandra, Sally G Hood, Lindsea C Booth, Song T Yao, Clive N. MayAbstract:Increased cardiac sympathetic nerve activity (CSNA) is a key feature of heart failure (HF) and is associated with poor outcome. There is evidence that central angiotensinergic mechanisms contribute to the increased CSNA in HF, but the central sites involved are unknown. In an ovine, rapid pacing model of HF, we investigated the contribution of the Lamina Terminalis and area postrema to the increased CSNA and also the responses to fourth ventricular infusion of the angiotensin type 1 receptor antagonist losartan. Ablation of the area postrema or sham lesion (n = 6/group), placement of Lamina Terminalis lesion electrodes (n = 5), and insertion of a cannula into the fourth ventricle (n = 6) were performed when ejection fraction was ~ 50%. When ejection fraction was < 40%, recording electrodes were implanted, and after 3 days, resting CSNA and baroreflex control of CSNA were measured before and following lesion of the Lamina Terminalis, in groups with lesion or sham lesion of the area postrema and before and following infusion of losartan (1.0 mg/h for 5 h) into the fourth ventricle. In conscious sheep with HF, lesion of the Lamina Terminalis did not significantly change CSNA (91 ± 2 vs. 86 ± 3 bursts/100 heart beats), whereas CSNA was reduced in the group with lesion of the area postrema (89 ± 3 to 45 ± 10 bursts/100 heart beats, P < 0.01) and following fourth ventricular infusion of losartan (89 ± 3 to 48 ± 8 bursts/100 heartbeats, P < 0.01). These findings indicate that the area postrema and brainstem angiotensinergic mechanisms may play an important role in determining the increased CSNA in HF.
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cortical activation and Lamina Terminalis functional connectivity during thirst and drinking in humans
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2011Co-Authors: Michael Farrell, Robin M. Mcallen, M J Mckinley, Tharushini K Bowala, Maria Gavrilescu, Paddy A Phillips, D A Denton, Gary F EganAbstract:The pattern of regional brain activation in humans during thirst associated with dehydration, increased blood osmolality, and decreased blood volume is not known. Furthermore, there is little information available about associations between activation in osmoreceptive brain regions such as the organum vasculosum of the Lamina Terminalis and the brain regions implicated in thirst and its satiation in humans. With the objective of investigating the neuroanatomical correlates of dehydration and activation in the ventral Lamina Terminalis, this study involved exercise-induced sweating in 15 people and measures of regional cerebral blood flow (rCBF) using a functional magnetic resonance imaging technique called pulsed arterial spin labeling. Regional brain activations during dehydration, thirst, and postdrinking were consistent with the network previously identified during systemic hypertonic infusions, thus providing further evidence that the network is involved in monitoring body fluid and the experience of thirst. rCBF measurements in the ventral Lamina Terminalis were correlated with whole brain rCBF measures to identify regions that correlated with the osmoreceptive region. Regions implicated in the experience of thirst were identified including cingulate cortex, prefrontal cortex, striatum, parahippocampus, and cerebellum. Furthermore, the correlation of rCBF between the ventral Lamina Terminalis and the cingulate cortex and insula was different for the states of thirst and recent drinking, suggesting that functional connectivity of the ventral Lamina Terminalis is a dynamic process influenced by hydration status and ingestive behavior.
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functional correlates of activity in neurons projecting from the Lamina Terminalis to the ventrolateral periaqueductal gray
European Journal of Neuroscience, 2009Co-Authors: Aaron Uschakov, Dennis Mcginty, Ronald Szymusiak, M J MckinleyAbstract:The Lamina Terminalis (LT) consists of the organum vasculosum of the LT (OVLT), the median preoptic nucleus (MnPO) and the subfornical organ (SFO). All subdivisions of the LT project to the ventrolateral periaqueductal gray (vlPAG). The LT and the vlPAG are implicated in several homeostatic and behavioral functions, including body fluid homeostasis, thermoregulation and the regulation of sleep and waking. By combining visualization of c-Fos protein and retrograde neuroanatomical tracer we have examined the functional correlates of LT-vlPAG projection neurons. Rats were injected with retrograde tracer into the vlPAG and, following a 1-week recovery period, they were subjected to either hypertonic saline administration (0.5 M NaCl, 1 mL/100 g i.p.), 24-h water deprivation, isoproterenol administration (increases circulating angiotensin II; 50 microg/kg s.c.), heat exposure (39 degrees C for 60 min) or permitted 180 min spontaneous sleep. Retrogradely labeled neurons from the vlPAG and double-labelled neurons were then identified and quantified throughout the LT. OVLT-vlPAG projection neurons were most responsive to hypertonic saline and water deprivation. SFO-vlPAG projection neurons were most active following isoproterenol administration, and MnPO-vlPAG projection neurons displayed significantly more Fos immunostaining following water deprivation, heat exposure and sleep. These results support the existence of functional subdivisions of LT-vlPAG-projecting neurons, and indicate three patterns of activity that correspond to thermal and sleep wake regulation, osmotic or hormonal stimuli.
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the trajectory of sensory pathways from the Lamina Terminalis to the insular and cingulate cortex a neuroanatomical framework for the generation of thirst
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2008Co-Authors: Jacob Harvey Hollis, M J Mckinley, Moyra Dsouza, Juliane Kampe, Brian J. OldfieldAbstract:The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex. After 2 days of infection, pseudorabies-positive neurons were identified within the thalamus and Lamina Terminalis. In a separate group of rats, the retrograde tracer cholera toxin subunit b (CTb) was used in combination with either isotonic (0.15 M NaCl) or hypertonic (0.8 M NaCl) saline (1 ml/100 g body wt ip). Rats injected with CTb in the insular cortex and stimulated with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the paraventricular, rhomboid, and reuniens thalamic nuclei, whereas those rats injected with CTb in the cingulate cortex and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the medial part of the mediodorsal, interanteromedial, anteromedial, and ventrolateral part of the laterodorsal thalamic nuclei. Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the Lamina Terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ. A small proportion of the CTb-positive neurons in the OVLT were immunopositive for transient receptor potential vanilloid 1, a putative osmoresponsive membrane protein. These results identify functional thalamocortical pathways involved in relaying osmotic signals to the insular and cingulate cortex and may provide a neuroanatomical framework for the emotional aspects of thirst.
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vasopressin secretion osmotic and hormonal regulation by the Lamina Terminalis
Journal of Neuroendocrinology, 2004Co-Authors: M J Mckinley, Robin M. Mcallen, Michael L Mathai, R C Mcclear, Richard R Miselis, G L Pennington, L Vivas, Johh D Wade, Brian J. OldfieldAbstract:The Lamina Terminalis, located in the anterior wall of the third ventricle, is comprised of the subfornical organ, median preoptic nucleus (MnPO) and organum vasculosum of the Lamina Terminalis (OVLT). The subfornical organ and OVLT are two of the brain's circumventricular organs that lack the blood–brain barrier, and are therefore exposed to the ionic and hormonal environment of the systemic circulation. Previous investigations in sheep and rats show that this region of the brain has a crucial role in osmoregulatory vasopressin secretion and thirst. The effects of lesions of the Lamina Terminalis, studies of immediate–early gene expression and electrophysiological data show that all three regions of the Lamina Terminalis are involved in osmoregulation. There is considerable evidence that physiological osmoreceptors subserving vasopressin release are located in the dorsal cap region of the OVLT and possibly also around the periphery of the subfornical organ and in the MnPO. The circulating peptide hormones angiotensin II and relaxin also have access to peptide specific receptors (AT1 and LGR7 receptors, respectively) in the subfornical organ and OVLT, and both angiotensin II and relaxin act on the subfornical organ to stimulate water drinking in the rat. Studies that combined neuroanatomical tracing and detection of c-fos expression in response to angiotensin II or relaxin suggest that both of these circulating peptides act on neurones within the dorsal cap of the OVLT and the periphery of the subfornical organ to stimulate vasopressin release.
Leo P Renaud - One of the best experts on this subject based on the ideXlab platform.
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presynaptic α adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum Lamina Terminalis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007Co-Authors: Miloslav Kolaj, Leo P RenaudAbstract:The median preoptic nucleus (MnPO) in the Lamina Terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole c...
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presynaptic α adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum Lamina Terminalis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007Co-Authors: Miloslav Kolaj, Leo P RenaudAbstract:The median preoptic nucleus (MnPO) in the Lamina Terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole cell patch-clamp recordings in rat brain slice preparations to evaluate the hypothesis that presynaptic adrenoceptors could modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine (NE; 20–50 μM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum Lamina Terminalis. These events were not correlated with any observed changes in membrane conductance arising from NE activity at postsynaptic α1- or α2-adrenoceptors. Consistent with a role for presynaptic α2-adrenoceptors, responses were selectively mimicked by an α2-adrenoceptor agonist (UK-14304) and blockable with an α2-adrenoceptor antagonist (idazoxan). Although the α1-adrenoceptor agonist cirazoline and the α1-adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE was noted to increase (via α1-adrenoceptors) or decrease (via α2-adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature IPSCs. Collectively, these observations imply that both presynaptic and postsynaptic α1- and α2-adrenoceptors in MnPO are capable of selective modulation of rapid GABAA receptor-mediated inhibitory synaptic transmission along the Lamina Terminalis and therefore likely to exert a prominent influence in regulating cell excitability within the MnPO.
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presynaptic gabab receptors modulate organum vasculosum Lamina Terminalis evoked postsynaptic currents in rat hypothalamic supraoptic neurons
Neuroscience, 2000Co-Authors: Miloslav Kolaj, C.r. Yang, Leo P RenaudAbstract:Abstract Whole-cell patch-clamp recordings obtained from 36 hypothalamic supraoptic nucleus neurons in explant preparations evaluated a role for GABA B receptors in modulating postsynaptic inhibitory and excitatory currents evoked by electrical stimulation in the organum vasculosum of the Lamina Terminalis. At a holding current of −65 mV, application of baclofen (1–10 μM) induced a dose-dependent reduction in the amplitude of pharmacologically isolated inhibitory and excitatory postsynaptic currents, converted paired-pulse depression in inhibitory postsynaptic currents to paired-pulse facilitation, and enhanced paired-pulse ratios for excitatory postsynaptic currents. In media containing 2-hydroxysaclofen (200–400 μM), baclofen-associated events were blocked and paired-pulse depression in evoked inhibitory postsynaptic currents was abolished. In addition, a progressive increase in the amplitude of inhibitory postsynaptic currents implied that GABA was endogenously active at presynaptic GABA B receptors. In contrast, no paired-pulse depression was observed for inhibitory postsynaptic currents evoked in six non-magnocellular neurons. Neither baclofen nor 2-hydroxysaclofen altered holding currents or input resistances in supraoptic neurons, or altered the kinetics of the evoked responses. These observations imply that the terminals of both inhibitory (GABAergic) and excitatory (glutamatergic) afferents to supraoptic nucleus neurons from organum vasculosum Lamina Terminalis neurons are subject to modulation by presynaptic GABA B receptors, and that this modulation is preferentially directed to the inhibitory inputs.
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organum vasculosum Lamina Terminalis evoked postsynaptic responses in rat supraoptic neurones in vitro
The Journal of Physiology, 1994Co-Authors: C.r. Yang, V V Senatorov, Leo P RenaudAbstract: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.
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membrane properties of organum vasculosum Lamina Terminalis neurons recorded in vitro
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1993Co-Authors: R Nissen, Charles W. Bourque, Leo P RenaudAbstract: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.
Charles W. Bourque - One of the best experts on this subject based on the ideXlab platform.
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hypertonicity sensing in organum vasculosum Lamina Terminalis neurons a mechanical process involving trpv1 but not trpv4
The Journal of Neuroscience, 2011Co-Authors: Sorana Ciura, Wolfgang Liedtke, Charles W. BourqueAbstract:Primary osmosensory neurons in the mouse organum vasculosum Lamina Terminalis (OVLT) transduce hypertonicity via the activation of nonselective cation channels that cause membrane depolarization and increased action potential discharge, and this effect is absent in mice lacking expression of the transient receptor potential vanilloid 1 (Trpv1) gene (Ciura and Bourque, 2006). However other experiments have indicated that channels encoded by Trpv4 also contribute to central osmosensation in mice (Liedtke and Friedman, 2003; Mizuno et al., 2003). At present, the mechanism by which hypertonicity modulates cation channels in OVLT neurons is unknown, and it remains unclear whether Trpv1 and Trpv4 both contribute to this process. Here, we show that physical shrinking is necessary and sufficient to mediate hypertonicity sensing in OVLT neurons isolated from adult mice. Steps coupling progressive decreases in cell volume to increased neuronal activity were quantitatively equivalent whether shrinking was evoked by osmotic pressure or mechanical aspiration. Finally, modulation of OVLT neurons by tonicity or mechanical stimulation was unaffected by deletion of trpv4 but was abolished in cells lacking Trpv1 or wild-type neurons treated with the TRPV1 antagonist SB366791. Thus, hypertonicity sensing is a mechanical process requiring Trpv1, but not Trpv4.
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mechanisms of osmotic and mechanical transduction in the organum vasculosum Lamina Terminalis
2011Co-Authors: Sorana Ciura, Charles W. BourqueAbstract:Mammals maintain a constant internal osmotic environment due to the existence of specialized osmosensory neurons which detect fluctuations in body fluid osmolality and can trigger homeostatic regulatory mechanisms to correct such deviations. The organum vasculosum of the Lamina Terminalis (OVLT) is the main osmosensory area of the brain. Despite its importance in whole body homeostasis, little is known about the electrophysiological properties of the OVLT. In this thesis we use murine OVLT neurons in isolation or in brain explants to study their osmosensory transduction properties. Hypertonic stimulation resulted in an increase in the cation conductance of the cells, the generation of an inward current and depolarization which triggered increased firing of action potentials. Two members of the TRPV family of channels, TRPV1 and TRPV4, were tested for their contribution to osmosensory transduction. We found that TRPV1, but not TRPV4, forms an osmotically gated channel in OVLT neurons. Absence of TRPV1 function, either through genetic engineering or pharmacological blockade, prevented the response of OVLT neurons to osmotic stimulation. In contrast, OVLT neurons obtained from Trpv4-/- mice showed normal osmosensitive responses. The transduction of hypertonic stimuli was found to be entirely mediated by the mechanical process associated with cellular shrinkage during the presentation of the stimulus. Previous studies have shown that osmosensory neurons are also able to detect other modes of stimulation, such as temperature. Here we show that TRPV1 enables osmosensory neurons in the supraoptic nucleus to respond to increases in external temperature. Another contributing factor to osmosensory detection are the glia surrounding osmosensory neurons which can release neuromodulatory factors during hypotonic stimulation. In this thesis we show that astrocytes in the OVLT can release glycine receptor agonists which cause hyperpolarization during a hypotonic stimulus, but this effect is secondary to the intrinsic ability of these neurons to detect such stimuli. In conclusion, OVLT neurons are intrinsic osmosensors equipped with stretch receptors encoded by Trpv1 functioning in the central control of body fluid homeostasis.%%%%Les mammiferes maintiennent l'osmolalite plasmatique pres d'une valeur constante grâce a lexistence de neurones osmosensoriels capables de detecter les fluctuations d`osmolalite fluidique et d'initier les mecanismes homeostatiques necessaires pour corriger ces deviations. L`Organum vasculosum Lamina Terminalis (OVLT) represente un site primaire pour l'osmoreception dans le systeme nerveux central. Meme si le role physiologique de cette structure est bien etabli, presque rien n'est connu au sujet des proprietes membranaires des neurones de l'OVLT qui sous-tendent la detection et le codage electrique des perturbations osmotiques. Nous avons utilise une approche electrophysiologique pour etudier les neurones de l`OVLT de souris suite a l'isolation in vitro ainsi que dans des tranches d'hypothalamus. La…
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axonal projections from the organum vasculosum Lamina Terminalis to the supraoptic nucleus functional analysis and presynaptic modulation
Clinical and Experimental Pharmacology and Physiology, 2001Co-Authors: Charles W. Bourque, Dominique RichardAbstract:SUMMARY 1. The rat organum vasculosum Lamina Terminalis (OVLT) contains GABA- and glutamate-releasing neurons that project directly to magnocellular neurosecretory cells (MNC) in the supraoptic nucleus. 2. Changes in osmolality over the OVLT in hypothalamic explants cause proportional changes in firing in MNC through corresponding changes in the frequency of spontaneous glutamatergic excitatory post-synaptic potentials without affecting GABAergic inhibitory post-synaptic potentials. 3. Exogenously applied atrial natriuretic peptide inhibits the osmotic control of MNC by causing a decrease in the amount of glutamate released provoked by action potentials originating from OVLT neurons.
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Circumventricular Organs: Gateways to the Brain Axonal Projections From The Organum Vasculosum Lamina Terminalis To The Supraoptic Nucleus: Functional Analysis And Presynaptic Modulation
Clinical and Experimental Pharmacology and Physiology, 2001Co-Authors: Charles W. Bourque, Dominique RichardAbstract:SUMMARY 1. The rat organum vasculosum Lamina Terminalis (OVLT) contains GABA- and glutamate-releasing neurons that project directly to magnocellular neurosecretory cells (MNC) in the supraoptic nucleus. 2. Changes in osmolality over the OVLT in hypothalamic explants cause proportional changes in firing in MNC through corresponding changes in the frequency of spontaneous glutamatergic excitatory post-synaptic potentials without affecting GABAergic inhibitory post-synaptic potentials. 3. Exogenously applied atrial natriuretic peptide inhibits the osmotic control of MNC by causing a decrease in the amount of glutamate released provoked by action potentials originating from OVLT neurons.
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membrane properties of organum vasculosum Lamina Terminalis neurons recorded in vitro
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1993Co-Authors: R Nissen, Charles W. Bourque, Leo P RenaudAbstract: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.
Miloslav Kolaj - One of the best experts on this subject based on the ideXlab platform.
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presynaptic α adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum Lamina Terminalis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007Co-Authors: Miloslav Kolaj, Leo P RenaudAbstract:The median preoptic nucleus (MnPO) in the Lamina Terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole cell patch-clamp recordings in rat brain slice preparations to evaluate the hypothesis that presynaptic adrenoceptors could modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine (NE; 20–50 μM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum Lamina Terminalis. These events were not correlated with any observed changes in membrane conductance arising from NE activity at postsynaptic α1- or α2-adrenoceptors. Consistent with a role for presynaptic α2-adrenoceptors, responses were selectively mimicked by an α2-adrenoceptor agonist (UK-14304) and blockable with an α2-adrenoceptor antagonist (idazoxan). Although the α1-adrenoceptor agonist cirazoline and the α1-adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE was noted to increase (via α1-adrenoceptors) or decrease (via α2-adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature IPSCs. Collectively, these observations imply that both presynaptic and postsynaptic α1- and α2-adrenoceptors in MnPO are capable of selective modulation of rapid GABAA receptor-mediated inhibitory synaptic transmission along the Lamina Terminalis and therefore likely to exert a prominent influence in regulating cell excitability within the MnPO.
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presynaptic α adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum Lamina Terminalis
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007Co-Authors: Miloslav Kolaj, Leo P RenaudAbstract:The median preoptic nucleus (MnPO) in the Lamina Terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole c...
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presynaptic gabab receptors modulate organum vasculosum Lamina Terminalis evoked postsynaptic currents in rat hypothalamic supraoptic neurons
Neuroscience, 2000Co-Authors: Miloslav Kolaj, C.r. Yang, Leo P RenaudAbstract:Abstract Whole-cell patch-clamp recordings obtained from 36 hypothalamic supraoptic nucleus neurons in explant preparations evaluated a role for GABA B receptors in modulating postsynaptic inhibitory and excitatory currents evoked by electrical stimulation in the organum vasculosum of the Lamina Terminalis. At a holding current of −65 mV, application of baclofen (1–10 μM) induced a dose-dependent reduction in the amplitude of pharmacologically isolated inhibitory and excitatory postsynaptic currents, converted paired-pulse depression in inhibitory postsynaptic currents to paired-pulse facilitation, and enhanced paired-pulse ratios for excitatory postsynaptic currents. In media containing 2-hydroxysaclofen (200–400 μM), baclofen-associated events were blocked and paired-pulse depression in evoked inhibitory postsynaptic currents was abolished. In addition, a progressive increase in the amplitude of inhibitory postsynaptic currents implied that GABA was endogenously active at presynaptic GABA B receptors. In contrast, no paired-pulse depression was observed for inhibitory postsynaptic currents evoked in six non-magnocellular neurons. Neither baclofen nor 2-hydroxysaclofen altered holding currents or input resistances in supraoptic neurons, or altered the kinetics of the evoked responses. These observations imply that the terminals of both inhibitory (GABAergic) and excitatory (glutamatergic) afferents to supraoptic nucleus neurons from organum vasculosum Lamina Terminalis neurons are subject to modulation by presynaptic GABA B receptors, and that this modulation is preferentially directed to the inhibitory inputs.
