Epileptogenesis is associated with enhanced glutamatergic transmission in the perforant path.
ABSTRACT The perforant path provides the main excitatory input into the hippocampus and has been proposed to play a critical role in the generation of temporal lobe seizures. It has been hypothesized that changes in glutamatergic transmission in this pathway promote the epileptogenic process and seizure generation. We therefore asked whether epileptogenesis is associated with enhanced glutamatergic transmission from the perforant path to dentate granule cells. We used a rat model of temporal lobe epilepsy in which spontaneous seizures occur after an episode of pilocarpine-induced status epilepticus. Whole cell patch-clamp recordings were obtained from dentate granule cells in hippocampal slices from control and epileptic animals 3 wk after pilocarpine-induced status epilepticus. The paired pulse ratio of perforant path-evoked AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) was reduced in tissue obtained from epileptic rats. This is consistent with an increase in release probability. N-methyl-d-aspartate (NMDA) receptor-mediated EPSCs were also prolonged. This prolongation could not be accounted for by decreased activity of glutamate transporters or by a change in NMDA receptor subunit composition in dentate granule cells, implying a change in NMDA receptor kinetics. This change in NMDA receptor kinetics was associated with the emergence of significant synaptic cross-talk, detected as a use-dependent block of receptors activated by medial perforant path synapses after lateral perforant path stimulation in MK-801. Enhanced glutamatergic transmission and the emergence of cross-talk among perforant path-dentate granule cell synapses may contribute to lowering seizure threshold.
Article: Genetics of temporal lobe epilepsy.[show abstract] [hide abstract]
ABSTRACT: The most common partial epilepsy, temporal lobe epilepsy (TLE) consists of a heterogeneous group of seizure disorders originating in the temporal lobe. TLE had been thought to develop as a result of acquired structural problems in the temporal lobe. During the past two decades, there has been growing evidence of the important influence of genetic factors, and familial and non-lesional TLE have been increasingly described. Here, we focus on the genetics of TLE and review related genes which have been studied recently. Although its molecular mechanisms are still poorly understood, TLE genetics is a fertile field, awaiting more research.Brain & development 11/2011; 34(8):609-16. · 1.74 Impact Factor