S. Charpier

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Niigata University

Sorbonne University

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Papers by S. Charpier

Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity

Journal of Neurophysiology, 1994

1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investi... more 1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency “oscillatory” field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M-cell collateral network. 3. Bursting cells were determined morphologi...

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Long-term potentiation of glycinergic inhibitory synaptic transmission

Journal of Neurophysiology, 1995

1. Tetanizing protocols were used to test whether glycinergic inhibition undergoes long-term plas... more 1. Tetanizing protocols were used to test whether glycinergic inhibition undergoes long-term plasticity in vivo. For this purpose we studied the inhibition evoked disynaptically in the teleost Mauthner (M) cell by stimulation of the posterior branch of the contralateral VIIIth nerve. The advantage of this experimental design is that the inhibition, which is mediated by identified second-order commissural interneurons, is not contaminated by parallel excitation. 2. The VIIIth-nerve-evoked inhibitory postsynaptic potentials (IPSPs), which are generated at the level of the soma, are depolarizing in Cl(-)-loaded M cells. After VIIIth nerve tetanization, these IPSPs exhibited potentiation lasting > 30 min in 23 of 31 cells. The maximum enhancement measured 5-10 min after the onset of the tetanization averaged 100 +/- 19% (mean +/- SE). In contrast, the non-"tetanized" collateral IPSP induced by antidromic stimulation of the M axon did not increase significantly suggesting sy...

Latent" inhibitory connections become functional during activity-dependent plasticity

Proceedings of the National Academy of Sciences, 1995

Simultaneous pre- and postsynaptic recordings from identified glycinergic inhibitory interneurons... more Simultaneous pre- and postsynaptic recordings from identified glycinergic inhibitory interneurons and the Mauthner cell showed that 25% of the afferents produced no or extremely small postsynaptic responses. Morphological determination of the number of contacts made by these cells on the Mauthner cell revealed a connectivity similar to that of functional neurons which always produce clear inhibitory postsynaptic potentials, suggesting that most of the endings, made by weak interneurons are silent. Intraaxonal injection of 4-aminopyridine or Ca2+ greatly enhanced transmission at functional connections but did not modify those which were ineffective. However, after eighth nerve tetanic stimuli, transmission at the weak connections was unmasked or enhanced for prolonged periods and was twice as likely to be potentiated, with a 6-fold greater mean enhancement than the potent ones. This result provides additional support for long-term potentiation of inhibitory synapses. Furthermore, wea...

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Slow modulations of high-frequency activity (40-140 Hz) discriminate preictal changes in human focal epilepsy

Scientific Reports, 2014

Recent evidence suggests that some seizures are preceded by preictal changes that start from minu... more Recent evidence suggests that some seizures are preceded by preictal changes that start from minutes to hours before an ictal event. Nevertheless an adequate statistical evaluation in a large database of continuous multiday recordings is still missing. Here, we investigated the existence of preictal changes in long-term intracranial recordings from 53 patients with intractable partial epilepsy (in total 531 days and 558 clinical seizures). We describe a measure of brain excitability based on the slow modulation of high-frequency gamma activities (40-140 Hz) in ensembles of intracranial contacts. In prospective tests, we found that this index identified preictal changes at levels above chance in 13.2% of the patients (7/53), suggesting that results may be significant for the whole group (p , 0.05). These results provide a demonstration that preictal states can be detected prospectively from EEG data. They advance understanding of the network dynamics leading to seizure and may help develop novel seizure prediction algorithms. n spite of available drug and surgical treatment options, a third of individuals with partial epilepsy have intractable seizures. The unpredictability of seizure occurrence limits their daily life, and underlies an enhanced risk of sudden unexpected death or morbidity 1 . Multiple quantitative analyses of the electroencephalogram (EEG) have aimed to define independent features and reproducible patterns that herald seizure onset 2-6 . Several studies have suggested that epileptic seizures do not occur randomly, but rather emerge from slow preictal changes in brain excitability that evolve over long timescales and predispose the brain to seizure 6 . In particular, a recent study -using intracranial electrodes connected to a telemetry unit implanted in ambulatory patientsshowed that a prospective seizure prediction is possible with the knowledge of the patient's pre-seizure EEG patterns 7 . In most of the investigated patients, the warning device can successfully identify seizure occurrences in advance (from minutes to hours) and at a level better than would be expected on the basis of chance alone. However, despite encouraging results, this study has been limited by the small number of patients and complex machine learning algorithms making difficult to explore possible underlying physiological mechanisms. Greater insights into the neuronal mechanisms of population behavior during the preictal period could not only improve seizure prediction but also help understand pathophysiological process of seizure initiation in the human brain . Recent wide-bandwidth records of local field potentials made with intracranial electrodes during presurgical evaluation have identified several new classes of electrographic activity at high-frequencies. These low-amplitude activities occur at frequencies .40 Hz, are confined to millimeter-scale tissue volumes, and thus are less visible and often confused with eye movement or muscle artifacts in standard scalp electroencephalography (EEG) . High-frequency activities, including gamma oscillations at 60-150 Hz and fast ripples at 250-500 Hz, have been associated with the initiation of epileptiform potentials and seizures in human temporal lobe and neocortical epilepsies . Furthermore, while high-frequency oscillations are present intermittently throughout interictal period , the occurrence of high-frequency activities increases significantly from several

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Different mechanisms of ripple-like oscillations in the human epileptic subiculum

Ann Neurol., 2014

Transient high-frequency oscillations (150-600 Hz) in local field potential generated by human hi... more Transient high-frequency oscillations (150-600 Hz) in local field potential generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of high-frequency oscillations (HFO) has been controversial. Here, we searched for HFOs in slices of the subiculum prepared from human hippocampal tissue resected for treatment of pharmacoresistant epilepsy. HFOs occurred spontaneously in extracellular field potentials during interictal discharges (IID) and also during pharmacologically induced preictal discharges (PID) preceding ictal-like events. While most of these events might be considered pathological since they invaded the fast ripple band (>250 Hz), others were spectrally similar to physiological ripples (150-250 Hz). Do similar cellular mechanisms underly IID-ripples and PID-ripples? Are ripple-like oscillations a valid proxy of epileptogenesis in human TLE? With combined intra-or juxta-cellular and extracellular recordings, we showed that, despite overlapping spectral components, ripple-like IID and PID oscillations were associated with different cellular and synaptic mechanisms. IID-ripples were associated with rhythmic GABAergic and glutamatergic synaptic potentials with moderate neuronal firing. In contrast, PID-ripples were associated with depolarizing synaptic inputs frequently reaching the threshold for bursting in most cells. Thus ripple-like oscillations (100-250 Hz) in the human epileptic hippocampus are associated with different mechanisms for synchrony reflecting distinct dynamic changes in inhibition and excitation during interictal and pre-ictal states.

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Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy

The Journal of Physiology, 1998

In vivo extracellular and intracellular recordings were performed from thalamocortical (TC) neuro... more In vivo extracellular and intracellular recordings were performed from thalamocortical (TC) neurones in a genetic model of absence epilepsy (genetic absence epilepsy rats from Strasbourg) during spontaneous spike and wave discharges (SWDs). Extracellularly recorded single units (n= 14) fired either a single action potential or a high frequency burst of up to three action potentials, concomitantly with the spike component of the spike‐wave complex. Three main events characterized the intracellular activity of twenty‐six out of twenty‐eight TC neurones during SWDs: a small amplitude tonic hyperpolarization that was present throughout the SWD, rhythmic sequences of EPSP/IPSPs occurring concomitantly with the spike‐wave complexes, and a small tonic depolarization at the end of the SWD. The rhythmic IPSPs, but not the tonic hyperpolarization, were mediated by activation of GABAA receptors since they reversed in polarity at ‐68 mV and appeared as depolarizing events when recording with KC...

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In vivo activity-dependent plasticity at cortico-striatal connections: Evidence for physiological long-term potentiation

Proceedings of the National Academy of Sciences, 1997

The purpose of the present study was to investigate in vivo the activity-dependent plasticity of ... more The purpose of the present study was to investigate in vivo the activity-dependent plasticity of glutamatergic cortico-striatal synapses. Electrical stimuli were applied in the facial motor cortex and intracellular recordings were performed in the ipsilateral striatal projection field of this cortical area. Recorded cells exhibited the typical intrinsic membrane properties of striatal output neurons and were identified morphologically as medium spiny type I neurons. Subthreshold cortical tetanization produced either shortterm posttetanic potentiation or short-term depression of cortically-evoked excitatory postsynaptic potentials. When coupled with a postsynaptic depolarization leading the membrane potential to a suprathreshold level, the tetanus induced long-term potentiation (LTP) of cortico-striatal synaptic transmission. Induction of striatal LTP was prevented by intracellular injection of a calcium chelator suggesting that this synaptic plasticity involves an increase of postsynaptic free calcium concentration. Contrasting with previous in vitro studies our findings demonstrate that LTP constitutes the normal form of use-dependent plasticity at cortico-striatal synapses. Since excitation of striatal neurons produces a disinhibition of premotor networks, LTP at excitatory striatal inputs should favor the initiation of movements and therefore could be critical for the functions of basal ganglia in motor learning.

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On the putative contribution of GABAB receptors to the electrical events occuring during spontaneous spike and wave discharges

by N. Leresche and S. Charpier

Neuropharmacology, 1999

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave d... more Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to −85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of −68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at − 55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA A and a GABA B IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA A and a GABA B IPSP, respectively. Our data indicate that there are no rhythmic GABA B IPSPs and low threshold Ca 2 + potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA B IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.

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Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity

Journal of Neurophysiology, 1994

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Long-term potentiation of glycinergic inhibitory synaptic transmission

Journal of Neurophysiology, 1995