Mauro Serafin - Academia.edu (original) (raw)
Papers by Mauro Serafin
The Journal of Neuroscience, 1997
Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by G-proteins can b... more Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by G-proteins can be transiently relieved (facilitated) by strong depolarizing prepulses. However, with respect to the physiological significance of facilitation, it remains to be established if it can be induced by action potentials (AP) in central neurons. With the use of whole-cell recordings of dissociated cholinergic basal forebrain neurons of the guinea pig, it is shown that the GTPγS-inhibited HVA currents that occur throughN-ethylmaleimide (NEM)-sensitive Gi–Gosubtypes of G-proteins can be facilitated. Furthermore, although different types of HVA channels are present in these neurons, facilitation occurred mostly through disinhibition of the N-type current. On the basis of data indicating that the recovery from facilitation was relatively slow, we tested if more physiological stimuli that crudely mimicked APs (2 msec long depolarizations to 40 mV from a holding of −50 mV) potentially could induce f...
The Journal of Neuroscience, 1997
The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhy... more The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhyperpolarizations (AHPs) of nucleus basalis (NB) cholinergic neurons were investigated in dissociated cells. Neurons with somata >25 μmwere studied because 80% of them stained positively for choline acetyltransferase and had electrophysiological characteristics identical to those of cholinergic NB neurons previously recorded in basal forebrain slices. Calcium currents of cholinergic NB neurons first were dissected pharmacologically into an amiloride-sensitive LVA and at least five subtypes of HVA currents. Approximately 17% of the total HVA current was sensitive to nifedipine (3 μm), 35% to ω-conotoxin-GVIA (200–400 nm), 10% to ω-Agatoxin-IVA (100 nm), and 20% to ω-Agatoxin-IVA (300–500 nm), suggesting the presence of L-, N-, P-, and Q-type channels, respectively. A remaining current (R-type) resistant to these antagonists was blocked by cadmium (100–200 μm). We then assessed pharmacol...
Routledge eBooks, Jun 1, 2023
Neuroscience, Jul 1, 1999
Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthe... more Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthectomy is a model of post-lesional plasticity in the central nervous system. Just after the removal of one labyrinth, the deafferented, ipsilateral vestibular nucleus neurons are almost silent, and the discharge of the contralateral vestibular nucleus neurons is increased. The associated static disorders disappear in a few days, as normal activity is restored in both vestibular nuclei. In this study, we searched for traces of vestibular compensation in isolated whole brains taken from adult guinea-pigs. The electrophysiological responses evoked in control brains were compared to those evoked in brains taken from animals that had previously been labyrinthectomized. Guineapigs compensated for an initial labyrinthectomy within three days. In vivo, subsequent deafferentation of vestibular nucleus neurons on the intact side triggered "Bechterew's phenomenon": a new postural and oculomotor syndrome appeared, similar to the one induced by the first lesion, but directed to the newly deafferented side. These disturbances would be caused by the new imbalance between the discharges of neurons in the two vestibular nuclei triggered by the second deafferentation. Experiments were designed to search for a similar imbalance in vitro in brains taken from labyrinthectomized animals, where the intact vestibular nerve is cut during the dissection. Isolated whole brains were obtained from young guinea-pigs at various times (one to seven days) following an initial labyrinthectomy. An imbalance between the resting activities of medial vestibular nucleus neurons on both sides of the brainstem was revealed in brains taken more than three days after the lesion: their discharge was higher on the compensated, initially lesioned side than on the newly deafferented side. In some cases, an oscillatory pattern of discharge, reminiscent of the spontaneous nystagmus associated in vivo with Bechterew's syndrome, appeared in both abducens nerves. These data demonstrate that most of the changes underlying vestibular compensation persist, and can thus be investigated in the isolated whole brain preparation. Brains removed only one day after the lesion displayed normal commissural responses and symmetric spinal inputs to vestibular nucleus neurons. However, an unusually large proportion of the neurons recorded on both sides of the preparation had very irregular spontaneous discharge rates. These data suggest that the first stages of vestibular compensation might be associated with transient changes in the membrane properties of vestibular nucleus neurons. Brains taken from compensated animals displayed a significant, bilateral decrease of the inhibitory commissural responses evoked in the medial vestibular nucleus by single-shock stimulation of the contralateral vestibular nerve. The sensitivity of abducens motoneurons on the initially lesioned, compensated side to synaptic activation from the contralesional vestibular nucleus neurons was also decreased. Both changes may explain the long-term, bilateral decrease of vestibular-related reflexes observed following unilateral labyrinthectomy. Spinal inputs to vestibular nucleus neurons became progressively asymmetric: their efficacy was increased on the lesioned side and decreased on the intact one. This last modification may support a functional substitution of the deficient, vestibular-related synergies involved in gaze and posture stabilization by neck-related reflexes.
European Journal of Neuroscience, Oct 1, 1998
The aim of the present study was to investigate whether the voltage‐dependent inhibition of calci... more The aim of the present study was to investigate whether the voltage‐dependent inhibition of calcium currents by serotonin 5‐HT1A agonists can be alleviated (facilitated) by action potential‐like depolarizations. In dissociated cholinergic basal forebrain neurons using whole‐cell recordings, it is shown that a selective serotonin 5‐HT1A agonist (8‐OH‐DPAT) predominantly blocks N‐type HVA calcium current, although a minor reduction of P‐type current was also observed. The inhibition may principally occur through Gi‐Go subtypes of G‐proteins because it was prevented by N‐ethylmaleimide, a substance known to block specifically pertussis‐sensitive G‐proteins. The inhibitory effect of 8‐OH‐DPAT on calcium currents is voltage‐dependent because it was alleviated by long‐lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made‐up of action potential‐like depolarizations that were given at a frequency of 200 Hz. This observation may have important implications during periods of high‐frequency rhythmic bursts, a firing pattern that is prevalent in cholinergic basal forebrain neurons.
The Journal of Neuroscience, Oct 1, 1997
<p>(A) In CC, as evident by subtraction of the current-voltage relationships obtained at vo... more <p>(A) In CC, as evident by subtraction of the current-voltage relationships obtained at voltages from −150 to +10 mV before (ACSF) and during application of clonidine at 10 µM, bath-application of clonidine did not elicit any current in hcrt/orx neurons. (B) In SDC, in contrast, subtraction of the currents measured in presence and absence of clonidine revealed a clonidine-dependent inward potassium current. Indeed, the inversion potential is around −55 mV which is the inversion potential of potassium in the experimental conditions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016672#s4" target="_blank">Methods</a>).</p
The Society for Neuroscience Abstracts, 1991
Cerebral Cortex, 2016
Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequenc... more Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells.
Frontiers in Neurology, 2016
Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previous... more Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wakepromoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters.
Information Processing Underlying Gaze Control, 1994
Information Processing Underlying Gaze Control, 1994
Multisensory Control of Posture, 1995
Journal of Neurophysiology
ABSTRACT
Neuroscience Letters, 1995
Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainst... more Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainstem slices, the effects of baclofen, a specific agonist of the metabotropic GABA B receptors, were tested on the three main types of MVNn (A, B and B + LTS MVNn) that were previously identified in this nucleus. Regardless of their type, almost all MVNn were hyperpolarized and inhibited by baclofen. These hyperpolarizing effect.,; persisted following either the addition of tetrodotoxin (TI~) in the perfusion medium, or in the presence of a high Mg2+/low Ca 2+ solution known to block synaptic transmission. These results demonstrate that all types of MVNn are endowed with postsynaptic GABA B receptors.
Neuroscience, 1996
A~tract-Gigantocellular neurons of the medullary nucleus gigantocellularis represent a major sour... more A~tract-Gigantocellular neurons of the medullary nucleus gigantocellularis represent a major source of reticulospinal pathways. Among other roles, they have been involved in the processing of vestibular information. The aim of the present study was to describe the major intrinsic membrane properties of these cells in guinea-pig brainstem slices. We found nucleus gigantocellularis neurons to be segregated in two cell types. Type A nucleus gigantocellularis neurons were characterized by the presence of a single large afterhyperpolarization and a potent transient 4-aminopyridine-sensitive rectification likely due to the presence of a transient outward potassium current. In contrast, type B nucleus gigantocellularis neurons had a narrower and faster rising action potential followed by an early fast and a delayed slower afterhyperpolarization. In contrast to type A neurons, type B neurons were, in addition, endowed with subthreshold tetrodotoxin-sensitive sodium-dependent plateau potentials. Whereas both cell types were endowed with high-threshold calcium-dependent action potentials, only type B nucleus gigantocellularis neurons also displayed long-lasting calcium-dependent plateau potentials. These results show that nucleus gigantocellularis neurons can be segregated by their intrinsic membrane properties in two cell types which are very similar to those that we have previously described in the medial vestibular nucleus. The possibility that these differences between type A and B neurons might play a role in the segregation between tonic and kinetic cells is discussed.
Experimental Brain Research, 1995
Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intra... more Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABA A receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg2+/low Ca 2+ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABA A receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABA A receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resuiting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.
European Journal of Neuroscience, 1998
The aim of the present study was to investigate whether the voltage‐dependent inhibition of calci... more The aim of the present study was to investigate whether the voltage‐dependent inhibition of calcium currents by serotonin 5‐HT1A agonists can be alleviated (facilitated) by action potential‐like depolarizations. In dissociated cholinergic basal forebrain neurons using whole‐cell recordings, it is shown that a selective serotonin 5‐HT1A agonist (8‐OH‐DPAT) predominantly blocks N‐type HVA calcium current, although a minor reduction of P‐type current was also observed. The inhibition may principally occur through Gi‐Go subtypes of G‐proteins because it was prevented by N‐ethylmaleimide, a substance known to block specifically pertussis‐sensitive G‐proteins. The inhibitory effect of 8‐OH‐DPAT on calcium currents is voltage‐dependent because it was alleviated by long‐lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made‐up of action potential‐like depolarizations that were given at a frequency of 200 Hz. This observation may have important...
European Journal of Neuroscience, 1996
The undecapeptide substance P (SP) has been recently implicated in the control of vestibular func... more The undecapeptide substance P (SP) has been recently implicated in the control of vestibular function. In particular, it seems to be co-localized with glutamate in approximately half of the primary vestibular afferents in mammals. Using intracellular recordings in guinea-pig brainstem slices, we have investigated the effects of SP and of several agonists of the three known tachykinin receptor subtypes (NK,, NK2 and NK3) on the three main types (A, B and B+LTS) of guinea-pig medial vestibular nucleus neurons (MVNn) that we had previously described. SP could induce two distinct kinds of effects on all types of MVNn. Whereas around half of them were depolarized and had their membrane resistance increased by SP,-1 0% of all MVNn were in contrast hyperpolarized and inhibited while their membrane resistance was decreased. Both responses persisted under conditions of blockade of synaptic transmission, and were thus due to the activation of postsynaptic binding sites. The SP-induced membrane depolarization could not be reproduced with any one of the specific agonists of the three tachykinin receptor subtypes, nor was it blocked by the specific NK1 receptor antagonists GR 82334 and CP 99994. This effect might therefore be due to the activation of a new, pharmacologically distinct, 'NK1-like' receptor. Only the hyperpolarizing effects, which were in contrast mimicked by the specific NK1 receptor agonists GR 73632 and [Sa$, Met (O,)"]-SP, would be mediated by the few typical NK1 receptors which have been demonstrated in the medial vestibular nucleus. Materials and methods Experiments were carried out on guinea-pig brainstem slices using standard techniques (see Serafin et al., 1991a, b). Animals weighing
The Journal of Neuroscience, 1997
Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by G-proteins can b... more Voltage-dependent inhibition of high voltage-activated (HVA) calcium currents by G-proteins can be transiently relieved (facilitated) by strong depolarizing prepulses. However, with respect to the physiological significance of facilitation, it remains to be established if it can be induced by action potentials (AP) in central neurons. With the use of whole-cell recordings of dissociated cholinergic basal forebrain neurons of the guinea pig, it is shown that the GTPγS-inhibited HVA currents that occur throughN-ethylmaleimide (NEM)-sensitive Gi–Gosubtypes of G-proteins can be facilitated. Furthermore, although different types of HVA channels are present in these neurons, facilitation occurred mostly through disinhibition of the N-type current. On the basis of data indicating that the recovery from facilitation was relatively slow, we tested if more physiological stimuli that crudely mimicked APs (2 msec long depolarizations to 40 mV from a holding of −50 mV) potentially could induce f...
The Journal of Neuroscience, 1997
The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhy... more The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhyperpolarizations (AHPs) of nucleus basalis (NB) cholinergic neurons were investigated in dissociated cells. Neurons with somata >25 μmwere studied because 80% of them stained positively for choline acetyltransferase and had electrophysiological characteristics identical to those of cholinergic NB neurons previously recorded in basal forebrain slices. Calcium currents of cholinergic NB neurons first were dissected pharmacologically into an amiloride-sensitive LVA and at least five subtypes of HVA currents. Approximately 17% of the total HVA current was sensitive to nifedipine (3 μm), 35% to ω-conotoxin-GVIA (200–400 nm), 10% to ω-Agatoxin-IVA (100 nm), and 20% to ω-Agatoxin-IVA (300–500 nm), suggesting the presence of L-, N-, P-, and Q-type channels, respectively. A remaining current (R-type) resistant to these antagonists was blocked by cadmium (100–200 μm). We then assessed pharmacol...
Routledge eBooks, Jun 1, 2023
Neuroscience, Jul 1, 1999
Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthe... more Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthectomy is a model of post-lesional plasticity in the central nervous system. Just after the removal of one labyrinth, the deafferented, ipsilateral vestibular nucleus neurons are almost silent, and the discharge of the contralateral vestibular nucleus neurons is increased. The associated static disorders disappear in a few days, as normal activity is restored in both vestibular nuclei. In this study, we searched for traces of vestibular compensation in isolated whole brains taken from adult guinea-pigs. The electrophysiological responses evoked in control brains were compared to those evoked in brains taken from animals that had previously been labyrinthectomized. Guineapigs compensated for an initial labyrinthectomy within three days. In vivo, subsequent deafferentation of vestibular nucleus neurons on the intact side triggered "Bechterew's phenomenon": a new postural and oculomotor syndrome appeared, similar to the one induced by the first lesion, but directed to the newly deafferented side. These disturbances would be caused by the new imbalance between the discharges of neurons in the two vestibular nuclei triggered by the second deafferentation. Experiments were designed to search for a similar imbalance in vitro in brains taken from labyrinthectomized animals, where the intact vestibular nerve is cut during the dissection. Isolated whole brains were obtained from young guinea-pigs at various times (one to seven days) following an initial labyrinthectomy. An imbalance between the resting activities of medial vestibular nucleus neurons on both sides of the brainstem was revealed in brains taken more than three days after the lesion: their discharge was higher on the compensated, initially lesioned side than on the newly deafferented side. In some cases, an oscillatory pattern of discharge, reminiscent of the spontaneous nystagmus associated in vivo with Bechterew's syndrome, appeared in both abducens nerves. These data demonstrate that most of the changes underlying vestibular compensation persist, and can thus be investigated in the isolated whole brain preparation. Brains removed only one day after the lesion displayed normal commissural responses and symmetric spinal inputs to vestibular nucleus neurons. However, an unusually large proportion of the neurons recorded on both sides of the preparation had very irregular spontaneous discharge rates. These data suggest that the first stages of vestibular compensation might be associated with transient changes in the membrane properties of vestibular nucleus neurons. Brains taken from compensated animals displayed a significant, bilateral decrease of the inhibitory commissural responses evoked in the medial vestibular nucleus by single-shock stimulation of the contralateral vestibular nerve. The sensitivity of abducens motoneurons on the initially lesioned, compensated side to synaptic activation from the contralesional vestibular nucleus neurons was also decreased. Both changes may explain the long-term, bilateral decrease of vestibular-related reflexes observed following unilateral labyrinthectomy. Spinal inputs to vestibular nucleus neurons became progressively asymmetric: their efficacy was increased on the lesioned side and decreased on the intact one. This last modification may support a functional substitution of the deficient, vestibular-related synergies involved in gaze and posture stabilization by neck-related reflexes.
European Journal of Neuroscience, Oct 1, 1998
The aim of the present study was to investigate whether the voltage‐dependent inhibition of calci... more The aim of the present study was to investigate whether the voltage‐dependent inhibition of calcium currents by serotonin 5‐HT1A agonists can be alleviated (facilitated) by action potential‐like depolarizations. In dissociated cholinergic basal forebrain neurons using whole‐cell recordings, it is shown that a selective serotonin 5‐HT1A agonist (8‐OH‐DPAT) predominantly blocks N‐type HVA calcium current, although a minor reduction of P‐type current was also observed. The inhibition may principally occur through Gi‐Go subtypes of G‐proteins because it was prevented by N‐ethylmaleimide, a substance known to block specifically pertussis‐sensitive G‐proteins. The inhibitory effect of 8‐OH‐DPAT on calcium currents is voltage‐dependent because it was alleviated by long‐lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made‐up of action potential‐like depolarizations that were given at a frequency of 200 Hz. This observation may have important implications during periods of high‐frequency rhythmic bursts, a firing pattern that is prevalent in cholinergic basal forebrain neurons.
The Journal of Neuroscience, Oct 1, 1997
<p>(A) In CC, as evident by subtraction of the current-voltage relationships obtained at vo... more <p>(A) In CC, as evident by subtraction of the current-voltage relationships obtained at voltages from −150 to +10 mV before (ACSF) and during application of clonidine at 10 µM, bath-application of clonidine did not elicit any current in hcrt/orx neurons. (B) In SDC, in contrast, subtraction of the currents measured in presence and absence of clonidine revealed a clonidine-dependent inward potassium current. Indeed, the inversion potential is around −55 mV which is the inversion potential of potassium in the experimental conditions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016672#s4" target="_blank">Methods</a>).</p
The Society for Neuroscience Abstracts, 1991
Cerebral Cortex, 2016
Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequenc... more Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells.
Frontiers in Neurology, 2016
Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previous... more Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wakepromoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters.
Information Processing Underlying Gaze Control, 1994
Information Processing Underlying Gaze Control, 1994
Multisensory Control of Posture, 1995
Journal of Neurophysiology
ABSTRACT
Neuroscience Letters, 1995
Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainst... more Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainstem slices, the effects of baclofen, a specific agonist of the metabotropic GABA B receptors, were tested on the three main types of MVNn (A, B and B + LTS MVNn) that were previously identified in this nucleus. Regardless of their type, almost all MVNn were hyperpolarized and inhibited by baclofen. These hyperpolarizing effect.,; persisted following either the addition of tetrodotoxin (TI~) in the perfusion medium, or in the presence of a high Mg2+/low Ca 2+ solution known to block synaptic transmission. These results demonstrate that all types of MVNn are endowed with postsynaptic GABA B receptors.
Neuroscience, 1996
A~tract-Gigantocellular neurons of the medullary nucleus gigantocellularis represent a major sour... more A~tract-Gigantocellular neurons of the medullary nucleus gigantocellularis represent a major source of reticulospinal pathways. Among other roles, they have been involved in the processing of vestibular information. The aim of the present study was to describe the major intrinsic membrane properties of these cells in guinea-pig brainstem slices. We found nucleus gigantocellularis neurons to be segregated in two cell types. Type A nucleus gigantocellularis neurons were characterized by the presence of a single large afterhyperpolarization and a potent transient 4-aminopyridine-sensitive rectification likely due to the presence of a transient outward potassium current. In contrast, type B nucleus gigantocellularis neurons had a narrower and faster rising action potential followed by an early fast and a delayed slower afterhyperpolarization. In contrast to type A neurons, type B neurons were, in addition, endowed with subthreshold tetrodotoxin-sensitive sodium-dependent plateau potentials. Whereas both cell types were endowed with high-threshold calcium-dependent action potentials, only type B nucleus gigantocellularis neurons also displayed long-lasting calcium-dependent plateau potentials. These results show that nucleus gigantocellularis neurons can be segregated by their intrinsic membrane properties in two cell types which are very similar to those that we have previously described in the medial vestibular nucleus. The possibility that these differences between type A and B neurons might play a role in the segregation between tonic and kinetic cells is discussed.
Experimental Brain Research, 1995
Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intra... more Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABA A receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg2+/low Ca 2+ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABA A receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABA A receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resuiting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.
European Journal of Neuroscience, 1998
The aim of the present study was to investigate whether the voltage‐dependent inhibition of calci... more The aim of the present study was to investigate whether the voltage‐dependent inhibition of calcium currents by serotonin 5‐HT1A agonists can be alleviated (facilitated) by action potential‐like depolarizations. In dissociated cholinergic basal forebrain neurons using whole‐cell recordings, it is shown that a selective serotonin 5‐HT1A agonist (8‐OH‐DPAT) predominantly blocks N‐type HVA calcium current, although a minor reduction of P‐type current was also observed. The inhibition may principally occur through Gi‐Go subtypes of G‐proteins because it was prevented by N‐ethylmaleimide, a substance known to block specifically pertussis‐sensitive G‐proteins. The inhibitory effect of 8‐OH‐DPAT on calcium currents is voltage‐dependent because it was alleviated by long‐lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made‐up of action potential‐like depolarizations that were given at a frequency of 200 Hz. This observation may have important...
European Journal of Neuroscience, 1996
The undecapeptide substance P (SP) has been recently implicated in the control of vestibular func... more The undecapeptide substance P (SP) has been recently implicated in the control of vestibular function. In particular, it seems to be co-localized with glutamate in approximately half of the primary vestibular afferents in mammals. Using intracellular recordings in guinea-pig brainstem slices, we have investigated the effects of SP and of several agonists of the three known tachykinin receptor subtypes (NK,, NK2 and NK3) on the three main types (A, B and B+LTS) of guinea-pig medial vestibular nucleus neurons (MVNn) that we had previously described. SP could induce two distinct kinds of effects on all types of MVNn. Whereas around half of them were depolarized and had their membrane resistance increased by SP,-1 0% of all MVNn were in contrast hyperpolarized and inhibited while their membrane resistance was decreased. Both responses persisted under conditions of blockade of synaptic transmission, and were thus due to the activation of postsynaptic binding sites. The SP-induced membrane depolarization could not be reproduced with any one of the specific agonists of the three tachykinin receptor subtypes, nor was it blocked by the specific NK1 receptor antagonists GR 82334 and CP 99994. This effect might therefore be due to the activation of a new, pharmacologically distinct, 'NK1-like' receptor. Only the hyperpolarizing effects, which were in contrast mimicked by the specific NK1 receptor agonists GR 73632 and [Sa$, Met (O,)"]-SP, would be mediated by the few typical NK1 receptors which have been demonstrated in the medial vestibular nucleus. Materials and methods Experiments were carried out on guinea-pig brainstem slices using standard techniques (see Serafin et al., 1991a, b). Animals weighing