Large frequency potentiation induced by 2 Hz stimulation in the hippocampus of epileptic El mice

Abstract

El mouse has been found to be characteristics with hippocampal disinhibition, and has been suggested decrease in GABAergic synaptic transmission [Ono et al., Brain Res. 745 (1997) 165–172; Fueta et al., Brain Res. 779 (1998) 324–328]. The efficacy of GABAergic synapses can be modulated in response to trains of low frequency stimulation. The frequency potentiation of a population spike (PS) and the field excitatory postsynaptic potential (fEPSP) induced by a low frequency stimulation (2 Hz for 15 s) were recorded for the CA3 subfield, and PS alone for the CA1 subfield and dentate gyrus. PS frequency potentiation was greater in El mice than in non-epileptic control ddY mice. Especially the CA3 subfield exhibited a high PS frequency potentiation (300±73%) compared to age-matched ddY mice (64±24%). However, EPSP frequency potentiation was similar in El and ddY mice. The degree of PS frequency potentiation in CA3 was decreased by the reduction of extracellular Ca 2+ from 2 to 1 mM in both strains, suggesting presynaptic involvement. The potentiation in El mice was suppressed by AMPA/kainate type receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX), but more than half of the control value remained at 5 μM, whereas the potentiation in ddY mice was abolished at this concentration. N-methyl- d-aspartate (NMDA) type receptor antagonist 3-3 (2-carboxypiperazine-4-yl) propyl-1-phosphonate (10 μM; CPP) did not affect the potentiation. Bicuculline (5 μM), GABA A receptor antagonist, did not increase the amplitude of PS during stimulation but induced epileptic (multiple PSs) potentials. High PS frequency potentiation of El mice was mimicked to the degree of that in ddY mice by a low dose of GABA B receptor agonist baclofen (3 μM). The suppression by baclofen was partially reversed by the antagonist saclofen (500 μM). The large frequency potentiation in young El mice, which do not have seizure-susceptibility, indicates an intrinsic property in El mice. It is suggested that the high synchronization of CA3 neurons in El mice is due to a little activation of GABA B receptor activation and also to enhancement of non-NMDA type synaptic transmission.