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


RESULTS
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 D₁/D₅ receptor blockade.


CONCLUSIONS
We conclude that chronic limbic epilepsy goes along also with functional alterations in extralimbic structures such as the striatum.
Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, Germany.
Yosef
Y
Avchalumov
Timo
T
Kirschstein
Rüdiger
R
Köhling
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D010862:Pilocarpine / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine