Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy

J Neurosci. 2009 Feb 11;29(6):1615-25. doi: 10.1523/JNEUROSCI.2081-08.2009.


Absence seizures are a leading form of childhood epilepsy. Human and mouse P/Q-type calcium channel gene mutations initiate a complex absence epilepsy and ataxia phenotype, and in mice, secondarily elevate neuronal low-voltage-activated T-type calcium currents. These currents influence thalamocortical network activity and contribute to the generation of cortical spike-wave discharges (SWDs) associated with absence seizures. To address whether enhanced thalamocortical T-type currents suffice to induce an epileptic phenotype, two BAC transgenic mouse lines overexpressing the Cacna1g gene for alpha1G T-type calcium channels were generated with low and high transgene copy numbers that exhibit elevated alpha1G expression and showed increased functional T-type currents measured in thalamic neurons. Both lines exhibit frequent bilateral cortical SWDs associated with behavioral arrest but lack other overt neurological abnormalities. These models provide the first evidence that primary elevation of brain T-type currents are causally related to pure absence epilepsy, and selectively identify Cacna1g, one of the three T-type calcium channel genes, as a key component of a genetically complex epileptogenic pathway.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / biosynthesis
  • Calcium Channels / genetics
  • Calcium Channels, T-Type / biosynthesis
  • Calcium Channels, T-Type / genetics*
  • Cerebral Cortex / physiology*
  • Epilepsy, Absence / etiology
  • Epilepsy, Absence / genetics*
  • Epilepsy, Absence / metabolism
  • Mice
  • Mice, Transgenic
  • Nerve Net / physiology*
  • Thalamus / physiology*


  • Cacna1g protein, mouse
  • Calcium Channels
  • Calcium Channels, T-Type