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Acta Physiologica 2011; Volume 203, Supplement 688
The 62nd National Congress of the Italian Physiological Society
9/25/2011-9/27/2011
Sorrento, Italy
ELECTROPHYSIOLOGICAL ANALYSIS OF THE HIPPOCAMPAL CIRCUIT IN THE RAC1/RAC3 DOUBLE KNOCKOUT MOUSE
Abstract number: P50
TALPO1 F, SPAIARDI1 P, TOSELLI1 M, DE CURTIS2 I, BIELLA1 GR
1Univ. of Pavia, Dept of Physiology, Pavia, Italy
2Cell Adhesion Unit, San Raffaele Scientific Institute and Univ. Vita-Salute San Raffaele, Milano, Italy
Rac1 and Rac3 are small GTPases co-expressed in mammalian brain. Double KO mice for Rac1 and Rac3 showed a drastic reduction of hilar mossy cells and of GABAergic interneurons in the dorsal hippocampus and an epileptic phenotype. In this work, using the patch-clamp technique applied to brain slices, we derived CA3 pyramidal neurons to test intrinsic and synaptic properties in double KO mice and to evaluate the epileptic threshold. First we analyzed the amplitude and the frequency of spontaneous EPSPs both in basal conditions and following bath application of 4-AP (50 ?M). No differences in EPSPs amplitude have been observed between Rac1N/Rac3KO (n=7) and control mice (n=6). However, EPSPs frequency increased significatively (t-test, p<0.05) from basal conditions in respect to events recorded after 4-AP perfusion. The increase in frequency was statistically higher in Rac1N/Rac3KO (+197%, n=7) than in control mice (+ 55%, n=6). The ability to elicit ictal-like epileptiform activity in CA3 following application of higher concentration of the convulsant 4-AP was also analyzed. Application of 4-AP 100 mM induced (in about 83% of neurons, n=6) ictal-like epileptiform activity in Rac1N/Rac3KO mice, but not in control mice (n=6). Application of 4-AP 500 mM induced ictal-like epileptiform activity both in Rac1N/Rac3KO mice (n=6) and in control mice (n=7). However, the time required to elicit an ictal-like discharges was shorter in Rac1N/Rac3KO mice (200 ? 0 s) than in control mice (466.67 ± 16.67 s). In conclusion these data indicate that the lack of Rac1 and Rac3 genes, produces an unbalance of the hippocampal excitability giving rise to a phenotype of hyperexcitability, likely due to an impairment in the migration of GABAergic interneurons.
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Acta Physiologica 2011; Volume 203, Supplement 688 :P50