Aberrant GABAA Receptor-Mediated Inhibition in Cortico-Thalamic Networks of Succinic Semialdehyde Dehydrogenase Deficient Mice

摘要: Aberrant γ-aminobutyric acid type A (GABAA) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined ‘phasic’ and ‘tonic’ GABAA thalamocortical neurons of somatosensory (ventrobasal, VB) thalamus, nucleus reticularis thalami (NRT) neurons, layer 5/6 pyramidal (barrel) cortex succinic semialdehyde dehydrogenase (SSADH) knock-out (SSADH−/−) mice that replicate human SSADH deficiency exhibit seizures. We found increased sIPSC frequency both VB NRT larger amplitude SSADH−/− compared to wild-type animals, demonstrating increase total phasic thalamus mice. mIPSCs were no different between genotypes, although there remained a trend toward more events In cortical sIPSCs fewer but mice, feature retained by mIPSCs. Tonic currents from WTs. These data show enhanced, rather than compromised, occurs agreement with previous studies, inhibitory gain-of-function may be common models seizures, could pathological importance patients deficiency.