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J Physiol Volume 578, Number 1, 193-211, January 1, 2007 DOI: 10.1113/jphysiol.2006.119297
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NEUROSCIENCE

Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region

Lynda El-Hassar1, Mathieu Milh1, Fabrice Wendling2, Nadine Ferrand1, Monique Esclapez1 and Christophe Bernard1

1 INMED-INSERM U29 – Université de la Méditerranée, 163 Route de Luminy BP13, 13273 Marseille Cedex 09, France
2 LTSI-INSERM U642, Campus de Beaulieu, 35042 Rennes Cedex, France

An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3–5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7–10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo. During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.

(Received 16 August 2006; accepted after revision 14 September 2006; first published online 28 September 2006)
Corresponding author C. Bernard: INSERM U751, Faculté de Médecine Timone, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France. Email: christophe.bernard{at}medecine.univ-mrs.fr




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