Dravet syndrome mice ( The α2/α3subunit 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 α2subunit expression. AZD7325 demonstrates seizure protective effects in
GABAAreceptor potentiators are commonly used for the treatment of epilepsy, but it is not clear whether targeting distinct GABAAreceptor subtypes will have disproportionate benefits over adverse effects. Here we demonstrate that the α2/α3selective positive allosteric modulator (PAM) AZD7325 preferentially potentiates hippocampal inhibitory responses at synapses proximal to the soma of CA1 neurons. The effect of AZD7325 on synaptic responses was more prominent in mice on the 129S6/SvEvTac background strain, which have been demonstrated to be seizure resistant in the model of Dravet syndrome (