Abstracts

Status epilepticus (SE) is often followed by severe cognitive impairment, including memory impairment. We have shown that SE is associated with impairment of single cells in the hippocampus that fire action potentials when the animal is in a specific location in space, the so-called place cells, and that place cell function correlates well with performance in tasks of visual-spatial memory. Place cell patterns therefore appear to be an excellent measure of spatial memory and may serve as a tool to assess seizure-induced impairment in memory. Here we determined the relationship between spatial memory and place cell function following SE. In addition, we determined if levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can improve cognitive function and place cell firing patterns when administered following SE., The study was designed to i) assess to relationship between learning and memory as measured in the Morris water maze with place cell firing patterns and histopathology in rats with and without a prior history of SE; and ii) determine whether LEV administered after SE alters subsequent outcome as measured by performance in the water maze, place cell function, and histopathology. Adult male rats were subjected to lithium-pilocarpine (Li-Pilo) SE at postnatal (P) day 70 (N=30) and then treated with LEV or normal saline (NS) for 14 days. Following discontinuation of the drug animals were studied in the water maze and then had electrodes placed and single units recorded starting at P120. Following the testing, brains were examined for cell loss using and mossy fiber sprouting., SE was associated with severely impaired performance in the water maze with SE rats demonstrating no learning over four days of testing. Paralleling this memory deficit was a marked disturbance in firing patterns of pyramidal neurons in CA1. Non-SE rats learned quickly over four days of water maze testing and had normal pyramidal cell firing patterns. LEV had no major effects on water maze performance or place cell function. Histopathological examination of the brains showed severe cell loss in CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV treatment resulted in less histological damage in the hippocampus but had no effect on spatial memorty function or place cell physiology in either control or SE rats., This study demonstrates that abnormalities in place cell firing patterns can be associated with adverse behavioral consequences. The profound deficit in pyramidal cell function in this study parallels the deficiencies in spatial memory seen in our rats. While LEV did not alter water maze performance, less cell loss was seen in animals receiving LEV than animals receiving NS. Because of the severity of the SE-induced it is quite likely that any subtle beneficial effect of LEV on cognition would not be apparent., (Supported by NINDS (Grants: NS27984 and NS44295) and a grant from UCB.)