Regional heterogeneity of pathophysiological alterations in CA1 and dentate gyrus in a chronic model of temporal lobe epilepsy.

摘要

1. Extracellular and intracellular recording techniques were employed in brain slice preparations to characterize responses of hippocampal tissue in the post-self sustaining limbic status epilepticus (post-SSLSE) model of chronic temporal lobe epilepsy (TLE) as compared with responses in slices from control animals. Experiments were performed > or = 1 mo, and up to 7 mo, after status epilepticus. Two regions of the hippocampal formation linked to different aspects of epileptogenesis, the CA1 region and the dentate gyrus (DG), were studied. In any given experiment, CA1 and DG were examined in different slices from the same animal. 2. Pyramidal cells in CA1 were activated by means of electrodes positioned over fiber bundles that monosynaptically project to these cells, either those located in the stratum lacunosum/moleculare or those in the stratum radiatum. Granule cells were similarly activated by electrodes positioned in the perforant path. Full input-output curves were determined by varying stimulus strength and charting the amplitudes of population spikes (PSs). 3. Two indexes, stimulus sensitivity and responsiveness, were quantified in control tissue and in post-SSLSE tissue by means of input-output curves to provide comparisons between normal and epileptic tissue. There were no changes in stimulus sensitivity, defined as the stimulus intensity required to evoke comparable responses in input-output curves, between control and post-SSLSE tissue. However, responsiveness, defined as the number of extracellular PSs or intracellular action potentials (APs) elicited by a stimulus strength giving rise to maximal-amplitude PSs, proved a reliable method for identifying and categorizing epileptic responses. This index allowed for comparisons between anatomic regions within an experiment as well as among experiments for the same region. Both CA1 pyramidal cells and DG granule cells from post-SSLSE tissue showed hyperresponsiveness relative to control tissue. 4. Control tissue never exhibited > 2 PSs in either CA1or DG in response to stimuli that produced maximal-amplitude PSs. Therefore a criterion of > or = 3 PSs was adopted to delineate tissue as hyperresponsive on the basis of extracellular responses. In CA1 about one half of the post-SSLSE slices displayed > or = 3 PSs with stimuli giving maximal-amplitude PSs, meeting the criterion for hyperresponsiveness; in DG about one fifth of the slices showed hyperresponsiveness. 5. CA1 and DG differed with respect to the spectrum of hyperresponsiveness they exhibited, this being more robust in CA1. The two regions studied also showed heterogeneity with respect to maximal PS amplitudes.(ABSTRACT TRUNCATED AT 400 WORDS)