title: Changes in inhibitory CA1 network in dual pathology model of epilepsy.
abstract: The combination of two precipitating factors appears to be more and more recognized in patients with temporal lobe epilepsy. Using a two-hit rat model, with a neonatal freeze lesion mimicking a focal cortical malformation combined with hyperthermia-induced seizures mimicking febrile seizures, we have previously reported an increase of inhibition in CA1 pyramidal cells at P20. Here, we investigated the changes affecting excitatory and inhibitory drive onto CA1 interneurons to better define the changes in CA1 inhibitory networks and their paradoxical role in epileptogenesis, using electrophysiological recordings in CA1 hippocampus from rat pups (16-20 d old). We investigated interneurons in CA1 hippocampal area located in stratum oriens (Or) and at the border of strata lacunosum and moleculare (L-M). Our results revealed an increase of the excitatory drive to both types of interneurons with no change in the inhibitory drive. The mechanisms underlying the increase of excitatory synaptic currents (EPSCs) in both types of interneurons are different. In Or interneurons, the amplitude of spontaneous and miniature EPSCs increased, while their frequency was not affected suggesting changes at the post-synaptic level. In L-M interneurons, the frequency of spontaneous EPSCs increases, but the amplitude is not affected. Analyses of miniature EPSCs showed no changes in both their frequency and amplitude. We concluded that L-M interneurons increase in excitatory drive is due to a change in Shaffer collateral axon excitability. The changes described here in CA1 inhibitory network may actually contribute to the epileptogenicity observed in this dual pathology model by increasing pyramidal cell synchronization.
authors.affiliation: Sainte-Justine Hospital Research Center, Université de Montréal, Montreal, QC, Canada. ouardouzm@hotmail.com
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ouardouz
authors.forename: Lionel
authors.initials: L
authors.lastname: Carmant
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley