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Jack A. Boulant - One of the best experts on this subject based on the ideXlab platform.
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Temperature effects on neuronal membrane potentials and inward currents in rat hypothalamic tissue slices.
The Journal of physiology, 2005Co-Authors: Yanmei Zhao, Jack A. BoulantAbstract:Preoptic-anterior hypothalamic (PO/AH) Neurones sense and regulate body temperature. Although controversial, it has been postulated that warm-induced depolarization determines neuronal thermosensitivity. Supporting this hypothesis, recent studies suggest that temperature-sensitive cationic channels (e.g. vanilloid receptor TRP channels) constitute the underlying mechanism of neuronal thermosensitivity. Moreover, earlier studies indicated that PO/AH neuronal warm sensitivity is due to depolarizing sodium currents that are sensitive to tetrodotoxin (TTX). To test these possibilities, intracellular recordings were made in rat hypothalamic tissue slices. Thermal effects on membrane potentials and currents were compared in PO/AH warm-sensitive, temperature-insensitive and Silent Neurones. All three types of Neurones displayed slight depolarization during warming and hyperpolarization during cooling. There were no significant differences in membrane potential thermosensitivity for the different neuronal types. Voltage clamp recordings (at -92 mV) measured the thermal effects on persistent inward cationic currents. In all Neurones, resting holding currents decreased during cooling and increased during warming, and there was no correlation between firing rate thermosensitivity and current thermosensitivity. To determine the thermosensitive contribution of persistent, TTX-sensitive currents, voltage clamp recordings were conducted in the presence of 0.5 microm TTX. TTX decreased the current thermosensitivity in most Neurones, but there were no resulting differences between the different neuronal types. The present study found no evidence of a resting ionic current that is unique to warm-sensitive Neurones. This supports studies suggesting that neuronal thermosensitivity is controlled, not by resting currents, but rather by currents that determine rapid changes in membrane potential between successive action potentials.
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Cellular mechanisms for neuronal thermosensitivity in the rat hypothalamus.
The Journal of Physiology, 1996Co-Authors: John Griffin, M L Kaple, A. R. Chow, Jack A. BoulantAbstract:1. To study the basic mechanisms of neuronal thermosensitivity, rat hypothalamic tissue slices were used to record and compare intracellular activity of temperature-sensitive and -insensitive Neurones. This study tested the hypothesis that different neuronal types have thermally dependent differences in the transient potentials that determine the interspike interval. 2. Most spontaneously firing Neurones displayed depolarizing prepotentials that preceded each action potential. In warm-sensitive Neurones, warming increased the rate of rise of the depolarizing prepotential which, in turn, decreased the interspike interval and increased the firing rate. In contrast, temperature had little or no effect on the rate of rise in prepotentials of temperature-insensitive Neurones. 3. Prepotential depolarization can be due to increasing depolarizing conductances or decreasing hyperpolarizing conductances. These are differences in the ionic conductances responsible for prepotentials in temperature-sensitive and -insensitive Neurones. In warm-sensitive Neurones, the net ionic conductance decreased as the prepotential depolarized towards threshold, suggesting that the prepotential is primarily determined by a decrease in outward potassium conductances. In contrast, in low-slope temperature-insensitive Neurones, the net conductance remained constant during the interspike interval, suggesting a more balanced combination of both depolarizing and hyperpolarizing conductances. 4. Transient outward potassium currents, including A-currents, are important determinants of neuronal firing rates. These currents were identified in all warm-sensitive Neurones tested, as well as in many temperature-insensitive and Silent Neurones. Since warming increased the rates of inactivation of these currents, transient K+ currents may contribute to the temperature-dependent prepotentials of some hypothalamic Neurones.
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Temperature effects on membrane potential and input resistance in rat hypothalamic Neurones.
The Journal of Physiology, 1995Co-Authors: John Griffin, Jack A. BoulantAbstract:1. Whole-cell recordings were conducted in rat hypothalamic tissue slices to test the hypothesis that thermal changes in membrane potential contribute to neuronal thermosensitivity. Intracellular recordings of membrane potential and input resistance were made in eighty-two Neurones, including twenty-four Silent Neurones and fifty-eight spontaneously firing Neurones (22 warm-sensitive Neurones and 36 temperature-insensitive Neurones). Fifty-seven of the Neurones were recorded in the preoptic and anterior hypothalamus. 2. Warm-sensitive Neurones increased their firing rates during increases in temperature (1.07 +/- 0.06 impulses s-1 degree C-1), but their resting membrane potentials were not affected by temperature (0.06 +/- 0.06 mV degree C-1). Similarly, temperature did not affect the membrane potentials of temperature-insensitive Neurones or Silent Neurones. 3. Silent Neurones had significantly lower input resistances (256.9 +/- 20.0 M omega), compared with temperature-insensitive (362.6 +/- 57.2 M omega) and warm-sensitive Neurones (392.2 +/- 50.0 M omega). Temperature had the same effect on all three types of Neurones, such that resistance increased during cooling and decreased during warming. 4. If hyperpolarizing or depolarizing holding currents were applied to Neurones, temperature caused changes in the membrane potentials. This spurious effect can be explained by thermally induced changes in the input resistance. 5. Measurements of electrode tip potentials indicated that artificial changes in membrane potential may also be recorded if grounding electrodes are not isolated from the changes in temperature. 6. These results suggest that physiological changes in resting membrane potentials do not determine neuronal warm sensitivity, and thermal changes in input resistance do not determine the primary differences between warm-sensitive and temperature-insensitive hypothalamic Neurones.
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Intracellular analysis of inherent and synaptic activity in hypothalamic thermosensitive Neurones in the rat.
The Journal of Physiology, 1991Co-Authors: M. C. Curras, Stephen R. Kelso, Jack A. BoulantAbstract:1. Intracellular neuronal activity was recorded in rat preoptic-anterior hypothalamic tissue slices. Thirty Neurones were classified as warm sensitive, cold sensitive or temperature insensitive, based on their firing rate response to temperature changes. Seventy-seven per cent of the Neurones were temperature insensitive, which included both spontaneously firing and Silent Neurones. Of all Neurones, 10% were warm sensitive and 13% were cold sensitive. 2. Silent temperature-insensitive Neurones had lower input resistances (126 +/- 21 M omega) than thermosensitive Neurones (179 +/- 24 M omega). Regardless of neuronal type, however, resistance was inversely related to temperature. 3. Warm-sensitive Neurones were characterized by a slow, depolarizing pre-potential, whose rate of rise was temperature dependent. This depolarizing potential disappeared during current-induced hyperpolarization, suggesting that intrinsic mechanisms are responsible for neuronal warm sensitivity. 4. Spike activity in cold-sensitive Neurones correlated with putative excitatory and inhibitory postsynaptic potentials, whose frequency was thermosensitive. This suggests that cold sensitivity in these Neurones depends on synaptic input from nearby Neurones. 5. Like cold-sensitive Neurones, action potentials of temperature-insensitive Neurones often were preceded by short duration (less than 20 ms), rapidly rising pre-potentials, whose rates of rise were not affected by temperature. In some temperature-insensitive Neurones, depolarizing current injection increased both firing rate (by 5-8 impulses s-1) and warm sensitivity, with pre-potentials having temperature-dependent rates of rise. We suggest that temperature-insensitive Neurones employ two opposing, thermally dependent mechanisms: a voltage-dependent depolarizing conductance and a hyperpolarizing sodium-potassium pump.
J H Coote - One of the best experts on this subject based on the ideXlab platform.
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The actions of 5-hydroxytryptamine on the membrane of putative sympatho-excitatory Neurones in the rostral ventrolateral medulla of the adult rat in vitro.
Brain research, 1993Co-Authors: D I Lewis, J H CooteAbstract:Intracellular recordings were obtained in vitro from Neurones lying within the rostral ventrolateral medulla of the adult rat. Neurones could be classified into three groups: Silent Neurones, irregularly firing Neurones which had a regular pattern of action-potential generation. Membrane hyperpolarization of regularly firing Neurones failed to reveal underlying EPSPs or disrupt the regular pattern of action-potential generation. Superfusion of a high Mg2+, low Ca2+ aCSF did not abolish action-potential generation but the regular pattern of firing of these Neurones was lost. 5-Hydroxytryptamine evoked a slow concentration-dependent hyperpolarization in both spontaneously active and Silent Neurones, accompanied by a decrease in cell-input resistance. This study has provided further evidence for pacemaker-like Neurones within the RVLM and for the modulation of these Neurones by 5-hydroxytryptamine.
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The actions of 5-hydroxytryptamine on the membrane of putative sympatho-excitatory Neurones in the rostral ventrolateral medulla of the adult rat in vitro.
Brain Research, 1993Co-Authors: D I Lewis, J H CooteAbstract:Abstract Intracellular recordings were obtained in vitro from Neurones lying within the rostral ventrolateral medulla of the adult rat. Neurones could be classified into three groups: Silent Neurones, irregularly firing Neurones and Neurones which had a regular pattern of action-potential generation. Membrane hyperpolarization of regularly firing Neurones failed to reveal underlying EPSPs or disrupt the regular pattern of action-potential generation. Superfusion of a high Mg2+, low Ca2+ aCSF did not abolish action-potential generation but the regular pattern of firing of these Neurones was lost. 5-Hydroxytryptamine evoked a slow concentration-dependent hyperpolarization in both spontaneously active and Silent Neurones, accompanied by a decrease in cell-input resistance. This study has provided further evidence for pacemaker-like Neurones within the RVLM and for the modulation of these Neurones by 5-hydroxytryptamine.
D Spanswick - One of the best experts on this subject based on the ideXlab platform.
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Electrophysiological properties of electrical synapses between rat sympathetic preganglionic Neurones in vitro.
The Journal of physiology, 1999Co-Authors: M F Nolan, S D Logan, D SpanswickAbstract:1. The electrophysiological properties of electrical synaptic transmission between sympathetic preganglionic Neurones (SPNs) in slices of rat spinal cord were investigated using simultaneous dual-electrode patch-clamp recordings. Electrotonic coupling was directly demonstrated between 21 pairs of SPNs. 2. Coupling coefficients determined from the steady-state response of both Neurones to current steps injected into either neurone ranged from 0. 02 to 0.48 (0.18 +/- 0.02, mean +/- s.e.m.). Synapses were bidirectional and symmetrical for the majority of connections with coupling coefficients similar in either direction. Asymmetrical coupling between a minority of cell pairs was due to differences in passive neuronal properties rather than rectification of the synaptic conductances. 3. Action potentials were manifest in adjoining cells as biphasic electrical postsynaptic potentials (ePSPs), composed of a rapid depolarising component followed by a more prolonged hyperpolarisation with amplitudes of 1.2 +/- 0.2 and 2.1 +/- 0.6 mV, respectively. 4. Postsynaptic potentials resembled low-pass filtered presynaptic spikes with frequency dependence determined by the junctional conductance and postsynaptic membrane properties. Increases in presynaptic action potential frequency caused attenuation of the hyperpolarising component of the ePSP that was attributed to shorter duration presynaptic spikes being more markedly filtered. 5. Synchronisation of spontaneous action potentials between electrotonically coupled Neurones was driven by subthreshold membrane potential activity resembling repetitive ePSPs. Synchronous spike firing in previously Silent Neurones could be driven by suprathreshold ePSPs induced by suprathreshold depolarisation of a single adjoining neurone. 6. These data characterise reliable communication of sub- and suprathreshold activity by electrical synapses enabling synchronised SPN firing which may contribute to generation of coherent sympathetic rhythms and promote summation of inputs to postganglionic Neurones.
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Electrophysiological properties of electrical synapses between rat sympathetic preganglionic Neurones in vitro.
The Journal of Physiology, 1999Co-Authors: M F Nolan, S D Logan, D SpanswickAbstract:The electrophysiological properties of electrical synaptic transmission between sympathetic preganglionic Neurones (SPNs) in slices of rat spinal cord were investigated using simultaneous dual-electrode patch-clamp recordings. Electrotonic coupling was directly demonstrated between 21 pairs of SPNs. Coupling coefficients determined from the steady-state response of both Neurones to current steps injected into either neurone ranged from 0.02 to 0.48 (0.18 ± 0.02, mean ± s.e.m.). Synapses were bidirectional and symmetrical for the majority of connections with coupling coefficients similar in either direction. Asymmetrical coupling between a minority of cell pairs was due to differences in passive neuronal properties rather than rectification of the synaptic conductances. Action potentials were manifest in adjoining cells as biphasic electrical postsynaptic potentials (ePSPs), composed of a rapid depolarising component followed by a more prolonged hyperpolarisation with amplitudes of 1.2 ± 0.2 and 2.1 ± 0.6 mV, respectively. Postsynaptic potentials resembled low-pass filtered presynaptic spikes with frequency dependence determined by the junctional conductance and postsynaptic membrane properties. Increases in presynaptic action potential frequency caused attenuation of the hyperpolarising component of the ePSP that was attributed to shorter duration presynaptic spikes being more markedly filtered. Synchronisation of spontaneous action potentials between electrotonically coupled Neurones was driven by subthreshold membrane potential activity resembling repetitive ePSPs. Synchronous spike firing in previously Silent Neurones could be driven by suprathreshold ePSPs induced by suprathreshold depolarisation of a single adjoining neurone. These data characterise reliable communication of sub- and suprathreshold activity by electrical synapses enabling synchronised SPN firing which may contribute to generation of coherent sympathetic rhythms and promote summation of inputs to postganglionic Neurones. Sympathetic preganglionic Neurones (SPNs) mediate the central sympathetic output to postganglionic Neurones in peripheral ganglia which in turn innervate target organs (Janig & McLachlan, 1992). The discharge of pre- and postganglionic sympathetic nerves in vivo includes synchronous rhythmic components which occur at frequencies of < 0.5 Hz, 2-6 Hz and approximately 10 Hz (Gebber, 1980; McAllen & Malpas, 1997; Malpas, 1998). Synchronisation of preganglionic activity may be required to enable summation of weak inputs to threshold for firing of postganglionic Neurones (Janig & McLachlan, 1992). Recordings of synchronous action potentials and subthreshold membrane potential oscillations from electrotonically coupled SPNs in vitro, suggest that electrical synapses between SPNs may contribute to generation of synchronous rhythmic patterns of sympathetic activity (Logan et al. 1996). However, an understanding of the cellular electrophysiological properties of electrical synaptic transmission between SPNs is necessary in order to determine how they may contribute to sympathetic output. Electrical synapses formed by gap junctions between Neurones mediate intercellular communication by allowing electrotonic flow of current directly from a presynaptic to a postsynaptic neurone (Llinas, 1985; Jefferys, 1995; Bennett, 1997). Electrophysiological and anatomical studies suggest the existence of electrical synapses between Neurones in the hippocampus, inferior olive, locus coeruleus, hypothalamus, and spinal cord (Llinas, 1985; Jefferys, 1995; Dermietzel, 1996). Electrical synapses allow reciprocal transfer of currents between Neurones and may therefore be able to mediate synchronisation of neuronal activity. For example, in the inferior olive, subthreshold membrane potential oscillations are synchronised by electrotonic coupling between Neurones resulting in synchronisation of climbing fibre inputs to cerebellar Purkinje cells (Llinas, 1985; Welsh & Llinas, 1997) and, in the hippocampus, axo-axonic coupling may mediate synchronised rhythmic action potential firing (Draguhn et al. 1998). In contrast to chemical synaptic transmission, the transfer of information between mammalian Neurones by electrical synapses is not well characterised. Properties such as the junctional conductance, voltage dependence, rectification, postsynaptic response to presynaptic action potentials and contribution of individual Neurones to synchronous network activity have been investigated using invertebrate and lower vertebrate preparations (Bennett, 1977, 1997) and by modelling electrotonically coupled Neurones (Traub, 1995; Vigmond et al. 1997; Marder, 1998), but have not been examined directly at electrical synapses between mammalian Neurones. In the present study we have focused on characterising these properties for electrical synapses between SPNs and on how the synaptic properties may contribute to the generation of synchronous neuronal activity. A preliminary account of part of this work has been published (Nolan et al. 1998).
D I Lewis - One of the best experts on this subject based on the ideXlab platform.
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The actions of 5-hydroxytryptamine on the membrane of putative sympatho-excitatory Neurones in the rostral ventrolateral medulla of the adult rat in vitro.
Brain research, 1993Co-Authors: D I Lewis, J H CooteAbstract:Intracellular recordings were obtained in vitro from Neurones lying within the rostral ventrolateral medulla of the adult rat. Neurones could be classified into three groups: Silent Neurones, irregularly firing Neurones which had a regular pattern of action-potential generation. Membrane hyperpolarization of regularly firing Neurones failed to reveal underlying EPSPs or disrupt the regular pattern of action-potential generation. Superfusion of a high Mg2+, low Ca2+ aCSF did not abolish action-potential generation but the regular pattern of firing of these Neurones was lost. 5-Hydroxytryptamine evoked a slow concentration-dependent hyperpolarization in both spontaneously active and Silent Neurones, accompanied by a decrease in cell-input resistance. This study has provided further evidence for pacemaker-like Neurones within the RVLM and for the modulation of these Neurones by 5-hydroxytryptamine.
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The actions of 5-hydroxytryptamine on the membrane of putative sympatho-excitatory Neurones in the rostral ventrolateral medulla of the adult rat in vitro.
Brain Research, 1993Co-Authors: D I Lewis, J H CooteAbstract:Abstract Intracellular recordings were obtained in vitro from Neurones lying within the rostral ventrolateral medulla of the adult rat. Neurones could be classified into three groups: Silent Neurones, irregularly firing Neurones and Neurones which had a regular pattern of action-potential generation. Membrane hyperpolarization of regularly firing Neurones failed to reveal underlying EPSPs or disrupt the regular pattern of action-potential generation. Superfusion of a high Mg2+, low Ca2+ aCSF did not abolish action-potential generation but the regular pattern of firing of these Neurones was lost. 5-Hydroxytryptamine evoked a slow concentration-dependent hyperpolarization in both spontaneously active and Silent Neurones, accompanied by a decrease in cell-input resistance. This study has provided further evidence for pacemaker-like Neurones within the RVLM and for the modulation of these Neurones by 5-hydroxytryptamine.
John N Wood - One of the best experts on this subject based on the ideXlab platform.
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gtp induced tetrodotoxin resistant na current regulates excitability in mouse and rat small diameter sensory Neurones
The Journal of Physiology, 2003Co-Authors: Mark D Baker, Sonia Y Chandra, Yanning Ding, Stephen G Waxman, John N WoodAbstract:Peripheral pain thresholds are regulated by the actions of inflammatory mediators. Some act through G-protein-coupled receptors on voltage-gated sodium channels. We have found that a low-threshold, persistent tetrodotoxin-resistant Na+ current, attributed to NaV1.9, is upregulated by GTP and its non-hydrolysable analogue GTP-γ-S, but not by GDP. Inclusion of GTP-γ-S (500 μm) in the internal solution led to an increase in maximal current amplitude of > 300 % within 5 min. In current clamp, upregulation of persistent current was associated with a more negative threshold for action potential induction (by 15–16 mV) assessed from a holding potential of −90 mV. This was not seen in Neurones without the low-threshold current or with internal GDP (P < 0.001). In addition, persistent current upregulation depolarized Neurones. At −60 mV, internal GTP-γ-S led to the generation of spontaneous activity in initially Silent Neurones only when persistent current was upregulated. These findings suggest that regulation of the persistent current has important consequences for nociceptor excitability.
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GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory Neurones
The Journal of Physiology, 2003Co-Authors: Mark D Baker, Sonia Y Chandra, Yanning Ding, Stephen G Waxman, John N WoodAbstract:Peripheral pain thresholds are regulated by the actions of inflammatory mediators. Some act through G-protein-coupled receptors on voltage-gated sodium channels. We have found that a low-threshold, persistent tetrodotoxin-resistant Na+ current, attributed to NaV1.9, is upregulated by GTP and its non-hydrolysable analogue GTP-γ-S, but not by GDP. Inclusion of GTP-γ-S (500 μm) in the internal solution led to an increase in maximal current amplitude of > 300 % within 5 min. In current clamp, upregulation of persistent current was associated with a more negative threshold for action potential induction (by 15–16 mV) assessed from a holding potential of −90 mV. This was not seen in Neurones without the low-threshold current or with internal GDP (P < 0.001). In addition, persistent current upregulation depolarized Neurones. At −60 mV, internal GTP-γ-S led to the generation of spontaneous activity in initially Silent Neurones only when persistent current was upregulated. These findings suggest that regulation of the persistent current has important consequences for nociceptor excitability.