Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels

Neuron. 2001 Jul 19;31(1):35-45. doi: 10.1016/s0896-6273(01)00343-9.


T-type Ca(2+) 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 alpha(1G) subunit of T-type Ca(2+) channels. The thalamocortical relay neurons of the alpha(1G)-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The alpha(1G)-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABA(B) receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by alpha(1G) T-type Ca(2+) channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / pharmacology
  • Animals
  • Baclofen / pharmacology
  • Calcium Channels, T-Type / deficiency
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / physiology*
  • Cerebral Cortex / physiology*
  • Cerebral Cortex / physiopathology
  • Electroencephalography
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / physiopathology*
  • Immunity, Innate / genetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology*
  • Protein Subunits
  • Receptors, GABA-B / physiology*
  • Seizures / genetics
  • Seizures / physiopathology*
  • Thalamic Nuclei / physiology
  • Thalamic Nuclei / physiopathology
  • Thalamus / physiology*
  • Thalamus / physiopathology


  • Calcium Channels, T-Type
  • Protein Subunits
  • Receptors, GABA-B
  • Baclofen
  • 4-Butyrolactone