Loss of GABAergic control of corticostriatal LTP following status epilepticus

The onset of spontaneous seizures in temporal lobe epilepsy is associated with an altered hippocampal circuitry. Neurochemical investigations have demonstrated that changes also occur in corticostriatal synaptic pathways. Since the striatum plays a major role in procedural learning, it is of particular interest whether dyskinetic motor dysfunction sometimes associated with epilepsy is indeed due to epilepsy-associated changes of basal ganglia function. Here, we analyzed corticostriatal long-term potentiation (LTP) in brain slices from pilocarpine-treated rats 4-10 weeks after status epilepticus. We stimulated corticostriatal fibers and recorded field potentials in the dorsomedial striatum. We found that LTP was significantly enhanced in slices from pilocarpine-treated rats as compared to control preparations. In chronically epileptic tissue, GABAA receptor blockade was not able to significantly enhance LTP any further. By contrast, in control slices it was able to strongly boost LTP. We conclude that epilepsy has a profound effect on the corticostriatal synaptic pathway, and that GABAA receptors lose their regulatory and suppressive role in synaptic plasticity in the dorsomedial striatum. Correspondence to: Rüdiger Köhling, Rostock University Medical Center, Oscar Langendorff Institute of Physiology, 18057 Rostock, Germany, Tel: +49-381-4948000, Fax: +49-381-494-8003, E-mail: [email protected]