Biomedical subjects

Gilles Huberfeld

Publications and source records attributed to Gilles Huberfeld.

4 recordsLinked to original sources

PubMed2006

Threshold behavior in the initiation of hippocampal population bursts.

Hippocampal population discharges such as sharp waves, epileptiform firing, and GDPs recur at long and variable intervals. The mechanisms for their precise timing are not well understood. Here, we show that population bursts in the disinhibited CA3 region are initiated at a threshold level of population firing after recovery from a previous event. Each population discharge follows an active buildup period when synaptic traffic and cell firing increase to threshold levels. Single-cell firing can advance burst onset by increasing population firing to suprathreshold values. Population synchrony is suppressed when threshold frequencies cannot be reached due to reduced cellular excitability or synaptic efficacy. Reducing synaptic strength reveals partially synchronous population bursts that are curtailed by GABA(B)-mediated conductances. Excitatory glutamatergic transmission and delayed GABA(B)-mediated signals have opposing feedback effects on CA3 cell firing and so determine threshold behavior for population synchrony.

Animals↗

PubMed2006

Ictal brain hyperperfusion contralateral to seizure onset: the SPECT mirror image.

PURPOSE: Ictal single-photon emission computed tomography (SPECT) may help localize the seizure-onset zone (SOZ) by detecting changes in regional cerebral blood flow induced by epileptic discharges. This imaging method also reveals hyperperfusions in areas of seizure propagation, including the hemisphere contralateral to the SOZ. We have studied the occurrence, the topography, and the clinical value of such contralateral ictal hyperperfusion areas (HPAs). METHODS: We examined data from presurgical evaluations of 36 consecutive patients with pharmacoresistant partial epilepsy of various localizations. Ictal and interictal SPECT examinations were made with 99mTc-ECD, and the scans were processed for coregistration, normalization, subtraction, and merging with MRI images. RESULTS: Contralateral HPAs were observed in 72% of the patients: 50% of mesiotemporal epilepsy cases with hippocampal sclerosis, 85.7% of the other mesiotemporal epilepsies, 85.7% of neocortical lateral temporal epilepsies, and 87.5% of extratemporal epilepsies. Contralateral HPAs were usually symmetrical to the SOZ, forming a mirror image, observed in 57.1% of the patients. They could be slightly asymmetrical in mesiotemporal epilepsies, perhaps because of the particular anatomic pathways linking temporal lobes. In neocortical epilepsies, they were located in the cortex homotopic to the SOZ. CONCLUSIONS: We show that the symmetrical nature of the mirror image usually does not disturb SPECT interpretation. It can confirm the location of the SOZ (11 patients) and even occasionally improve the precision of its definition (nine patients) by restraining several potential SOZ-related HPAs to a single one or by permitting a restricted localization of the SOZ in a large HPA.

Brain↗

PubMed2005

Emergence of disinhibition-induced synchrony in the CA3 region of the guinea pig hippocampus in vitro.

Suppressing inhibition mediated by GABAA receptors induces rhythmic bursts of synchronous firing in the CA3 region of the hippocampus. Extracellular and intracellular records were made from guinea pig hippocampal slices to examine the emergence of this synchrony. We found that application of GABAA receptor antagonists initiated a sequence of changes in the activity of the CA3 neuronal population. First, the frequency of firing detected in multiunit records increased. Then, firing began to oscillate with increases followed by decreases in firing that occurred at intervals of 0.5-2 s. The coherence of the rhythmic activity at a single site increased with time, and discharges at distant sites in the CA3 region became correlated. Fluctuations in firing were associated with extracellular field potentials. Finally, epileptiform events associated with large field potentials began to recur at intervals of 5-10 s. The onset of fully synchronous events was sudden and correlated with a large increase in the amplitude of the field potential. Thus the CA3 population can express states of partial population synchrony preceding the onset of epileptiform discharges. A similar activity was induced and maintained by applying low doses of GABAA receptor antagonists. Intracellular records suggest that inhibitory signalling mediated by GABAB receptors contributes to the emergence of this activity. States of partial synchrony in the CA3 region exposed to GABAA receptor antagonists therefore depend on alternating periods of firing, presumably dependent on excitatory synaptic mechanisms, and silence, mediated in part by the activation of GABAB receptors.

Action Potentials↗

PubMed2004

Fever, genes, and epilepsy.

About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever.

Epilepsy↗