Neuronal computation and temporal coding in epileptic rat – Epileptic-Code

Temporal Lobe Epilepsy (TLE) is the most common form of partial epilepsy in adults (30'40% of all forms of epilepsies). It is now well accepted that hippocampus plays a key role in the pathophysiology of TLE. It has been shown that, in human patients and animal models of TLE, an important rewiring of its neuronal circuit occurs. One of the best examples of network reorganisation is the mossy fibers sprouting that establish novel aberrant glutamatergic synapses onto granule cells in the hippocampus (Represa et al., 1989;Tauck and Nadler, 1985;Sutula et al., 1989), leading to a recurrent excitatory circuit that contributes to seizures. Beyond seizures, TLE is often associated with pronounced cognitive impairments (Hermann et al., 1997;Helmstaedter, 2002;Liu et al., 2003), but little is known about the mechanisms underlying such alterations (Holmes, 2005). Hence the paramount importance to determine, outside the manifestation of seizure, whether aberrant synapses may impact the computational properties of neurons in the epileptic brain. Toward this aim we will have two complementary approaches: an in vitro and in vivo approach. The in vitro approach, performed in hippocampal slice, will allow will allow the investigation of basic computational features of epileptic dentate granule cells, notably in term of their input-output operation, and firing properties. In vivo, we will use a novel technology for intracellular recordings in behaving animals that offers the unique opportunity to directly assess coding alterations under natural conditions and to directly link subthreshold inputs, received by a given cell, with its output in an awaked freely moving animal. In conclusion, our proposal aims to shed light on cellular mechanisms involved in neurological disorder notably by elucidating the alteration of processing of neuronal information in epileptic tissue using a wide panel of complementary and novel approaches.