Synaptic changes in GABAA receptor expression in the thalamus of the stargazer mouse model of absence epilepsy.

Absence seizures are known to result from disturbances within the cortico-thalamocortical network, which remains partially synchronous under normal conditions but switches to a state of hypersynchronicity and hyperexcitability during absence seizures. There is evidence to suggest that impaired GABAergic inhibitory function within the thalamus could contribute to the generation of hypersynchronous oscillations in some animal models of absence epilepsy. Recently, we demonstrated region-specific alterations in the tissue expression level of GABAA receptors (GABA(A)Rs) α1 and β2 subunits within the thalamus of the stargazer mouse model of absence epilepsy. In the present study we investigated whether changes in these subunits also occur at synapses in the ventral posterior (VP) complex where they are components of phasic GABA(A)R receptors. Postembedding immunogold cytochemistry and electron microscopy were used to analyze the relative synaptic expression of α1 and β2 subunits in the VP thalamic region in epileptic stargazer mice compared to their non-epileptic littermates. We show that there is a significant increase in expression of α1 and β2 subunits (53.6% and 45.8%, respectively) at synapses in the VP region of stargazers, indicative of an increase in phasic GABA(A)Rs at thalamocortical (TC) relay neurons. Furthermore, we investigated whether tissue expression of GABA(A)R subunits α4 and δ, which constitute part of tonic GABA(A)Rs in the VP region, is altered in the stargazer mouse. Semi-quantitative Western blotting showed a significant increase in GABA(A)R α4 and δ subunits in the VP region of stargazer thalamus, which would indicate an increase in tonic GABA(A)R expression. Our findings show that there are changes in the levels of both phasic and tonic GABA(A)Rs in the VP thalamus; altered GABAergic inhibition within the VP could be one of many mechanisms contributing to the generation of absence seizures in this model.

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