Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels

T-type Ca2+ currents have been proposed to be involved in the genesis of spike-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 α1G subunit of T-type Ca2+ channels. The thalamocortical relay neurons of the α1G-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The α1G-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABAB receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by α1G T-type Ca2+ channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.