Cortical expression of AMPA receptors during postnatal development in a genetic model of absence epilepsy.

Childhood absence epilepsy has been associated with poor academic performance, behavioural difficulties, as well as increased risk of physical injury in some affected children. The frequent episodes of 'absence' arise from corticothalamocortical network dysfunction, with multifactorial mechanisms potentially involved in genetically different patients. Aberrations in glutamatergic neurotransmission has been implicated in some seizure models, and we have recently reported that reduced cortical AMPA receptor (AMPAR) expression (predominantly GluA4- containing AMPARs) in parvalbumin-containing (PV+ ) inhibitory interneurons, could underlie seizure generation in the stargazer mutant mouse. In the present study, we investigate AMPA receptor subunit changes occurring during postnatal development in the stargazer mouse, to determine when these changes occur relative to seizure onset and thus could be contributory to seizure generation. Using quantitative western blotting, we analysed the expression of AMPAR GluA1-4 subunits in the somatosensory cortex at three critical time points; two before seizure onset (postnatal days (PN) 7-9 and 13-15), and one at seizure onset (PN17-18) in stargazers. We report that compared to their non-epileptic littermates, in the stargazer somatosensory cortex, there was a significant reduction in expression of AMPARs containing GluA1, 3 and 4 subunits prior to seizure onset, whereas reduction in expression of GluA2-AMPARs appears to be a post-seizure event. Thus, while loss of GluA4-containing AMPARs (likely GluA1/4 and GluA3/4) may be linked to seizure induction, the loss of GluA2-containing AMPARs is a secondary post-seizure mechanism, which is most likely involved in seizure maintenance.