NMDA Receptor Expression in the Thalamus of the Stargazer Model of Absence Epilepsy

In the stargazer mouse model of absence epilepsy, altered corticothalamic excitation of reticular thalamic nucleus (RTN) neurons has been suggested to contribute to abnormal synchronicity in the corticothalamic-thalamocortical circuit, leading to spike-wave discharges, the hallmark of absence seizures. AMPA receptor expression and function are decreased in stargazer RTN, due to a mutation of AMPAR auxiliary subunit stargazin. It is unresolved and debated, however, if decreased excitation of RTN is compatible with epileptogenesis. We tested the hypothesis that relative NMDAR expression may be increased in RTN and/or thalamic synapses in stargazers using Western blot on dissected thalamic nuclei and biochemically isolated synapses, as well as immunogold cytochemistry in RTN. Expression of main NMDAR subunits was variable in stargazer RTN and relay thalamus; however, mean expression values were not statistically significantly different compared to controls. Furthermore, no systematic changes in synaptic NMDAR levels could be detected in stargazer thalamus. In contrast, AMPAR subunits were markedly decreased in both nucleus-specific and synaptic preparations. Thus, defective AMPAR trafficking in stargazer thalamus does not appear to lead to a ubiquitous compensatory increase in total and synaptic NMDAR expression, suggesting that elevated NMDAR function is not mediated by changes in protein expression in stargazer mice.