Abstracts

RRATIONALE: Experimental microgyri (MG) are enriched in inhibitory cells that express high levels of non-NMDA receptors (Jacobs et al 1999 Epi Res, 36:165). We hypothesize that enhanced inhibition may contribute to the lack of epileptiform activity within the MG in comparison to the adjacent epileptogenic paramicrogyral zone (PMZ). NMDA receptor antagonists block the PMZ epileptiform activity (Jacobs et al 1999 J Neurophysiol, 81:159), suggesting a possible role for enhanced NMDA-mediated excitation. To test these possibilities, we examined paired-pulse inhibition and the contribution of NMDA receptors to the short latency field potential (FP). METHODS: We recorded from in vitro slices from adult rats in which neonatal freeze lesions had produced a MG, or from homologous control tissue. In each slice a razor cut was made to separate the MG and PMZ. FPs were recorded simultaneously within layer II of MG and PMZ in response to stimulation ~250 ?m away from each recording electrode. Pairs of stimuli were given at 20-450 ms intervals. Amino-5-phosphonovaleric acid (APV;50-100 ?M) was bath-applied. Results reported as mean?SEM, with t-tests, p<0.05. RESULTS:_With paired MG stimuli (intervals 160-300 ms), peak negativity of the second FP was suppressed by 13-16%. This paired-pulse inhibition was significantly greater than that in PMZ or control cortex (at 200 ms interval, %of first response: 84?3, 102?4 and 95?3% for 9 MG, 9 PMZ and 13 controls, respectively). Inhibition is known to abbreviate cortical FPs, thus the duration of the FP negativity may be an indicator of the level of intracortical inhibition. Short latency FPs recorded from MG were significantly briefer than those from PMZ or control cortex (half-width: 4.3?0.7, 7.1?0.6 and 6.6?0.5 ms for 17 MG, 17 PMZ and 10 controls). APV application reduced the peak FP significantly more in PMZ than in either MG or controls (%change: 42?7, 18?7 and 20?7% in 12 PMZ, 12 MG and 14 controls). CONCLUSIONS: Results suggest that inhibition in microgyri is especially strong, while the adjacent epileptogenic zone contains an enhancement of the NMDA-dependent field potential. Supported by NIH grants NS12151 and NS06477 from the NINDS.