Altered physiology and pharmacology in the corticostriatal system in a model of temporal lobe epilepsy

P>Purpose: Temporal lobe epilepsy (TLE) is associated with changes in hippocampal function/morphology. These changes often manifest as a decline in cognitive abilities, which in animal models is reflected in reduced spatial learning and up-regulation or down-regulation of synaptic plasticity. Beyond this, however, changes also occur in other, extralimbic structures, as has been shown on the neurochemical level. Here, our aim was to test whether functional changes occur also in corticostriatal synaptic communication, also because the striatum is instrumental in motor planning and coordination and hence serves important nonlimbic functions. Methods: We analyzed corticostriatal long-term potentiation (LTP) in brain slices of pilocarpine-treated rats after status epilepticus (SE). To determine whether chronic seizures, or SE itself, impact basal ganglia function, tissue was investigated (1) shortly after SE (3-5 days, acute group), and (2) after chronic epilepsy had been established (chronic group, 4-10 weeks after SE). Key Findings: Early after SE, only little synaptic plasticity emerged. In the chronic group, however, LTP was enhanced significantly in the SE group versus control preparations. Using pharmacologic blockade of N-methyl-d-aspartate (NMDA) receptors, LTP in chronically epileptic tissue could be dissected into an early, NMDA-dependent and a late, NMDA-independent phase, which reverted to LTD with additional dopamine D-1/D-5 receptor blockade. Significance: We conclude that chronic limbic epilepsy goes along also with functional alterations in extralimbic structures such as the striatum.