Abstracts

The entorhinal cortex (EC), and specifically its layer V, receives projections from the subiculum. While both of these structures have been implicated in mesial temporal lobe epilepsy, surgical removal of the EC can control seizure activity. The majority of [italic]in vitro[/italic] investigations have demonstrated EC hyperexcitability by utilizing pharmacological agents; however, these studies involved control tissue. To this end, we assess the network activity within the pilocarpine treated EC in the absence of convulsants., Adult male Sprague Dawley rats were injected with pilocarpine (380 mg/kg, i.p.) to induce status epilepticus, while age matched non epileptic controls (NEC) were injected with saline. Following a latent period, pilocarpine treated rats displayed chronic seizures. Intracellular sharp (3M Potassium acetate) and field potential electrodes (ACSF) were used to assess EC activity in combined hippocampal [ndash] EC slices (450 mm)., We observed spontaneous (duration = 2.60 [plusmn] 0.49 s; interval of occurrence = 35.05 [plusmn] 4.35 s; n=31) and stimulus induced (duration = 2.50 [plusmn] 0.68 s; n=33) [italic]in vitro[/italic] epileptiform activity in the pilocaprine treated EC, but this did not occur in the NEC (n=26). These [italic]in vitro[/italic] epileptiform events displayed bidirectional routes of propagation (n=8) within the two subdivisions of the EC, and network interactions within EC superficial layers (n=8). We did not attribute this hyperexcitability to a change in the intrinsic firing properties of EC neurons as we obtained an overwhelming population of regular firing neurons (NEC: 20/26, Pilocarpine: 64/76) versus the number of intrinsic bursters (NEC: 6/26, Pilocarpine: 6/76). Futhermore, at the intracellular level, single shock activation with minimal stimulus intensity within the NEC and pilocarpine treated EC produced two contrasting results. Extracellular stimulation at resting membrane potential in NEC slices, elicited a depolarizing post-synaptic response (n=27/27), which was rarely observed in pilocarpine treated tissue (8/75). In contrast to the NEC, the pilocarpinei treated EC exhibited spontaneous (50/75) and stimulus induced (56/75) paroxysmal activity. This spontaneous (n=5) and stimulus induced bursting (n=5) was resilient to the NR2B antagonist ifenprofil (10 mM). Non-specific antagonism of NMDA receptors (CPP = 10 mM) produced an enhanced duration of stimulus induced epileptiform activity (n= 6) as well as continued spontaneous synaptic bursting (n=4). Subsequent application of CNQX (10 mM) blocked [italic]in vitro[/italic] epileptiform activity (n=6)., We demonstrate that the deep layers of the pilocarpine treated EC is hyperexcitable and may exhibit perturbations in NMDA receptor function., (Supported by Savoy Foundation.)