• David E Naylor and Claude G Wasterlain.
• Department of Neurology, Veterans Administration Greater Los Angeles Healthcare Center and University of California at Los Angeles, Los Angeles, California 90073, USA. dnaylor@ucla.edu
• Epilepsia. 2005 Jan 1; 46 Suppl 5: 142-7.

PurposeTo study the pharmacologic and synaptic basis for the early loss of paired-pulse inhibition that occurs in the perforant-path stimulation model of status epilepticus.MethodsHippocampal slices were prepared from male Wistar rats. Test paired pulses (20- to 50-ms interstimulus interval) of the perforant path were used before and after an abbreviated period of perforant-path stimulation (1-5 min; 2-Hz continuous with 20 Hz of 10 s/min pulses) while either recording field potentials from the dentate gyrus granule cell layer or directly measuring whole-cell patch-clamp currents from granule cells. Paired-pulse field recordings also were obtained during perfusion of the gamma-aminobutyric acid (GABA)(A) antagonist bicuculline.ResultsProlonged loss of paired-pulse inhibition occurs after brief (< 5 min) perforant-path stimulation in vitro (similar to results in vivo) with the paired-pulse population spike amplitude ratio (P2/P1) increasing from a baseline of 0.53 +/- 0.29 to 1.17 +/- 0.09 after perforant-path stimulation (p < 0.05). After perfusion with the GABA(A) antagonist, bicuculline, the P2/P1 ratio also increased from a baseline of 0.52 +/- 0.16 to 1.15 +/- 0.26 (p < 0.05). After 1-2 min of perforant-path stimulation, a 22 +/- 6% (p < 0.05) decrease occurred in the P2/P1 amplitude ratio of paired-pulse evoked inhibitory postsynaptic currents.ConclusionsSimilar to in vivo, loss of paired-pulse inhibition occurs with brief perforant-path stimulation in vitro. GABA(A) antagonism causes a similar loss of paired-pulse inhibition, and the effects of perforant-path stimulation on postsynaptic inhibitory currents also are consistent with the involvement of GABA(A) synaptic receptors. The findings suggest that loss of inhibition at GABA synapses may be an important early event in the initiation of status epilepticus.

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