E. Idoux - Academia.edu (original) (raw)

Papers by E. Idoux

Research paper thumbnail of The Vestibular System

The Rat Nervous System, 2015

Research paper thumbnail of Developmental regulation of the membrane properties of central vestibular neurons by sensory vestibular information in the mouse

The Journal of Physiology, 2007

The effect of the lack of vestibular input on the membrane properties of central vestibular neuro... more The effect of the lack of vestibular input on the membrane properties of central vestibular neurons was studied by using a strain of transgenic, vestibular-deficient mutant KCNE1 −/− mice where the hair cells of the inner ear degenerate just after birth. Despite the absence of sensory vestibular input, their central vestibular pathways are intact. Juvenile and adult homozygous mutant have a normal resting posture, but show a constant head bobbing behaviour and display the shaker/waltzer phenotype characterized by rapid bilateral circling during locomotion. In juvenile mice, the KCNE1 mutation was associated with a strong decrease in the expression of the calcium-binding proteins calbindin, calretinin and parvalbumin within the medial vestibular nucleus (MVN) and important modifications of the membrane properties of MVN neurons. In adult mice, however, there was almost no difference between the membrane properties of MVN neurons of homozygous and control or heterozygous mutant mice, which have normal inner ear hair cells and show no behavioural symptoms. The expression levels of calbindin and calretinin were lower in adult homozygous mutant animals, but the amount of calcium-binding proteins expressed in the MVN was much greater than in juvenile mice. These data demonstrate that suppression of sensory vestibular inputs during a 'sensitive period' around birth can generate the circling/waltzing behaviour, but that this behaviour is not due to persistent abnormalities of the membrane properties of central vestibular neurons. Altogether, maturation of the membrane properties of central vestibular neurons is delayed, but not impaired by the absence of sensory vestibular information.

Research paper thumbnail of Control of Local Intracellular Calcium Concentration with Dynamic-Clamp Controlled 2-Photon Uncaging

PLoS ONE, 2011

The variations of the intracellular concentration of calcium ion ([Ca 2+ ] i ) are at the heart o... more The variations of the intracellular concentration of calcium ion ([Ca 2+ ] i ) are at the heart of intracellular signaling, and their imaging is therefore of enormous interest. However, passive [Ca 2+ ] i imaging provides no control over these variations, meaning that a full exploration of the functional consequences of [Ca 2+ ] i changes is difficult to attain. The tools designed so far to modify [Ca 2+ ] i , even qualitatively, suffer drawbacks that undermine their widespread use. Here, we describe an electrooptical technique to quantitatively set [Ca 2+ ] i , in real time and with sub-cellular resolution, using two-photon Ca 2+ uncaging and dynamic-clamp. We experimentally demonstrate, on neurons from acute olfactory bulb slices of Long Evans rats, various capabilities of this technique previously difficult to achieve, such as the independent control of the membrane potential and [Ca 2+ ] i variations, the functional knocking-in of user-defined virtual voltage-dependent Ca 2+ channels, and the standardization of [Ca 2+ ] i patterns across different cells. Our goal is to lay the groundwork for this technique and establish it as a new and versatile tool for the study of cell signaling.

Research paper thumbnail of Evidence against a role of gap junctions in vestibular compensation

Neuroscience Letters, 2009

Vestibular compensation following unilateral labyrinthectomy is associated with modifications of ... more Vestibular compensation following unilateral labyrinthectomy is associated with modifications of the membrane and firing properties of central vestibular neurons. To determine whether gap junctions could be involved in this process, immunofluorescent detection of neuronal connexin 36 and astrocytic connexin 43 was performed in the medial vestibular nucleus (MVN) of rats. In non-lesioned animals, strong staining was observed with anti-connexin 43 antibodies, while moderate staining was obtained with the anti-connexin 36 antibody. However, the expression of either type of connexin was not modified following unilateral labyrinthectomy. These morphological observations were complemented by pharmacological tests performed during extracellular recordings of MVN neurons in guinea pig brainstem slices. In non-lesioned animals, the gap junction blocker carbenoxolone reversibly decreased or suppressed the spontaneous discharge of about 60% of MVN neurons. This reduction was often associated with a long-duration disruption of the regularity of spike discharge. Both effects were mimicked by several other gap junction blockers, but not by glycyrrhizic acid, an analog of carbenoxolone that does not block gap junctions but reproduces its non-specific effects, nor by the selective inhibitor of astrocytic connexin-based networks endothelin-1. Similar effects of carbenoxolone were obtained on the spontaneous activity of ipsilesional MVN neurons recorded in brainstem slices taken from labyrinthectomized animals. Altogether, these results suggest that neuronal gapjunctions are involved in shaping the spontaneous activity of MVN neurons. However, unilateral labyrinthectomy does not affect the expression of gap junctions in vestibular nuclei nor their implication in the regulation of neuronal activity.

Research paper thumbnail of Control of Neuronal Persistent Activity by Voltage-Dependent Dendritic Properties

Journal of Neurophysiology, 2008

LE. Control of neuronal persistent activity by voltage-dependent dendritic properties. . Neural i... more LE. Control of neuronal persistent activity by voltage-dependent dendritic properties. . Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamicclamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.

Research paper thumbnail of Static and Dynamic Membrane Properties of Lateral Vestibular Nucleus Neurons in Guinea Pig Brain Stem Slices

Journal of Neurophysiology, 2003

Static and dynamic membrane properties of lateral vestibular nucleus neurons in guinea pig brain ... more Static and dynamic membrane properties of lateral vestibular nucleus neurons in guinea pig brain stem slices. . In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and type B neurons identified in the MVN. Unlike MVN neurons (MVNn), the giant-size LVN neurons (LVNn) form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVNn, but also an A-like rectification like type A MVNn. In accordance with their lower membrane resistance, the sensitivity of LVNn to current injection was lower than that of MVNn over a large range of frequencies. The main difference between LVNn and MVNn was that the Bode plots showing the sensitivity of LVNn as a function of stimulation frequency were flatter than those of MVNn, and displayed a weaker resonance. Furthermore, most LVNn did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVNn. LVNn synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, whereas the giant LVNn that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVNn and MVNn may reflect their specific physiological roles.

Research paper thumbnail of Intrinsic membrane properties of central vestibular neurons in rodents

Experimental Brain Research, 2011

Numerous studies in rodents have shown that the functional eYcacy of several neurotransmitter rec... more Numerous studies in rodents have shown that the functional eYcacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modiWed during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deWcient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modiWcations in the distribution of these neurons into diVerent neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and Wnally, (3) the intracellular calcium concentration has a major eVect on the intrinsic membrane properties of central vestibular neurons.

Research paper thumbnail of Oscillatory and Intrinsic Membrane Properties of Guinea Pig Nucleus Prepositus Hypoglossi Neurons In Vitro

Journal of Neurophysiology, 2006

Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleu... more Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in ϳ25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively smallamplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.

Research paper thumbnail of The Vestibular System

The Rat Nervous System, 2015

Research paper thumbnail of Developmental regulation of the membrane properties of central vestibular neurons by sensory vestibular information in the mouse

The Journal of Physiology, 2007

The effect of the lack of vestibular input on the membrane properties of central vestibular neuro... more The effect of the lack of vestibular input on the membrane properties of central vestibular neurons was studied by using a strain of transgenic, vestibular-deficient mutant KCNE1 −/− mice where the hair cells of the inner ear degenerate just after birth. Despite the absence of sensory vestibular input, their central vestibular pathways are intact. Juvenile and adult homozygous mutant have a normal resting posture, but show a constant head bobbing behaviour and display the shaker/waltzer phenotype characterized by rapid bilateral circling during locomotion. In juvenile mice, the KCNE1 mutation was associated with a strong decrease in the expression of the calcium-binding proteins calbindin, calretinin and parvalbumin within the medial vestibular nucleus (MVN) and important modifications of the membrane properties of MVN neurons. In adult mice, however, there was almost no difference between the membrane properties of MVN neurons of homozygous and control or heterozygous mutant mice, which have normal inner ear hair cells and show no behavioural symptoms. The expression levels of calbindin and calretinin were lower in adult homozygous mutant animals, but the amount of calcium-binding proteins expressed in the MVN was much greater than in juvenile mice. These data demonstrate that suppression of sensory vestibular inputs during a 'sensitive period' around birth can generate the circling/waltzing behaviour, but that this behaviour is not due to persistent abnormalities of the membrane properties of central vestibular neurons. Altogether, maturation of the membrane properties of central vestibular neurons is delayed, but not impaired by the absence of sensory vestibular information.

Research paper thumbnail of Control of Local Intracellular Calcium Concentration with Dynamic-Clamp Controlled 2-Photon Uncaging

PLoS ONE, 2011

The variations of the intracellular concentration of calcium ion ([Ca 2+ ] i ) are at the heart o... more The variations of the intracellular concentration of calcium ion ([Ca 2+ ] i ) are at the heart of intracellular signaling, and their imaging is therefore of enormous interest. However, passive [Ca 2+ ] i imaging provides no control over these variations, meaning that a full exploration of the functional consequences of [Ca 2+ ] i changes is difficult to attain. The tools designed so far to modify [Ca 2+ ] i , even qualitatively, suffer drawbacks that undermine their widespread use. Here, we describe an electrooptical technique to quantitatively set [Ca 2+ ] i , in real time and with sub-cellular resolution, using two-photon Ca 2+ uncaging and dynamic-clamp. We experimentally demonstrate, on neurons from acute olfactory bulb slices of Long Evans rats, various capabilities of this technique previously difficult to achieve, such as the independent control of the membrane potential and [Ca 2+ ] i variations, the functional knocking-in of user-defined virtual voltage-dependent Ca 2+ channels, and the standardization of [Ca 2+ ] i patterns across different cells. Our goal is to lay the groundwork for this technique and establish it as a new and versatile tool for the study of cell signaling.

Research paper thumbnail of Evidence against a role of gap junctions in vestibular compensation

Neuroscience Letters, 2009

Vestibular compensation following unilateral labyrinthectomy is associated with modifications of ... more Vestibular compensation following unilateral labyrinthectomy is associated with modifications of the membrane and firing properties of central vestibular neurons. To determine whether gap junctions could be involved in this process, immunofluorescent detection of neuronal connexin 36 and astrocytic connexin 43 was performed in the medial vestibular nucleus (MVN) of rats. In non-lesioned animals, strong staining was observed with anti-connexin 43 antibodies, while moderate staining was obtained with the anti-connexin 36 antibody. However, the expression of either type of connexin was not modified following unilateral labyrinthectomy. These morphological observations were complemented by pharmacological tests performed during extracellular recordings of MVN neurons in guinea pig brainstem slices. In non-lesioned animals, the gap junction blocker carbenoxolone reversibly decreased or suppressed the spontaneous discharge of about 60% of MVN neurons. This reduction was often associated with a long-duration disruption of the regularity of spike discharge. Both effects were mimicked by several other gap junction blockers, but not by glycyrrhizic acid, an analog of carbenoxolone that does not block gap junctions but reproduces its non-specific effects, nor by the selective inhibitor of astrocytic connexin-based networks endothelin-1. Similar effects of carbenoxolone were obtained on the spontaneous activity of ipsilesional MVN neurons recorded in brainstem slices taken from labyrinthectomized animals. Altogether, these results suggest that neuronal gapjunctions are involved in shaping the spontaneous activity of MVN neurons. However, unilateral labyrinthectomy does not affect the expression of gap junctions in vestibular nuclei nor their implication in the regulation of neuronal activity.

Research paper thumbnail of Control of Neuronal Persistent Activity by Voltage-Dependent Dendritic Properties

Journal of Neurophysiology, 2008

LE. Control of neuronal persistent activity by voltage-dependent dendritic properties. . Neural i... more LE. Control of neuronal persistent activity by voltage-dependent dendritic properties. . Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamicclamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.

Research paper thumbnail of Static and Dynamic Membrane Properties of Lateral Vestibular Nucleus Neurons in Guinea Pig Brain Stem Slices

Journal of Neurophysiology, 2003

Static and dynamic membrane properties of lateral vestibular nucleus neurons in guinea pig brain ... more Static and dynamic membrane properties of lateral vestibular nucleus neurons in guinea pig brain stem slices. . In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and type B neurons identified in the MVN. Unlike MVN neurons (MVNn), the giant-size LVN neurons (LVNn) form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVNn, but also an A-like rectification like type A MVNn. In accordance with their lower membrane resistance, the sensitivity of LVNn to current injection was lower than that of MVNn over a large range of frequencies. The main difference between LVNn and MVNn was that the Bode plots showing the sensitivity of LVNn as a function of stimulation frequency were flatter than those of MVNn, and displayed a weaker resonance. Furthermore, most LVNn did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVNn. LVNn synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, whereas the giant LVNn that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVNn and MVNn may reflect their specific physiological roles.

Research paper thumbnail of Intrinsic membrane properties of central vestibular neurons in rodents

Experimental Brain Research, 2011

Numerous studies in rodents have shown that the functional eYcacy of several neurotransmitter rec... more Numerous studies in rodents have shown that the functional eYcacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modiWed during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deWcient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modiWcations in the distribution of these neurons into diVerent neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and Wnally, (3) the intracellular calcium concentration has a major eVect on the intrinsic membrane properties of central vestibular neurons.

Research paper thumbnail of Oscillatory and Intrinsic Membrane Properties of Guinea Pig Nucleus Prepositus Hypoglossi Neurons In Vitro

Journal of Neurophysiology, 2006

Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleu... more Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in ϳ25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively smallamplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.