The Journal of Physiology | 2019
Potentiating α2 subunit containing perisomatic GABAA receptors protects against seizures in a mouse model of Dravet syndrome
Abstract
Dravet syndrome mice (Scn1a+/−) demonstrate a marked strain dependence for the severity of seizures which is correlated with GABAA receptor α2 subunit expression. The α2/α3 subunit selective positive allosteric modulator (PAM) AZD7325 potentiates inhibitory postsynaptic currents (IPSCs) specifically in perisomatic synapses. AZD7325 demonstrates stronger effects on IPSCs in the seizure resistant mouse strain, consistent with higher α2 subunit expression. AZD7325 demonstrates seizure protective effects in Scn1a+/− mice without apparent sedative effects in vivo.