Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca2+ channels

T-type Ca2+ currents have been proposed to be involved in the genesis of sp ike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question , we generated a null mutation of the alpha (1G) subunit of T-type Ca2+ cha nnels. The thalamocortical relay neurons of the alpha (1G)-deficient mice l acked the burst mode firing of action potentials, whereas they showed the n ormal pattern of tonic mode firing. The alpha (1G)-deficient thalamus was s pecifically resistant to the generation of spike-and-wave discharges in res ponse to GABA(B) receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by alpha (1G) T-type Ca2+ channels plays a critica l role in the genesis of absence seizures in the thalamocortical pathway.