The γ2 subunit of GABA_A receptors is required for maintenance of receptors at mature synapses

The γ2 subunit of GABA_A receptor chloride channels is required for normal channel function and for postsynaptic clustering of these receptors during synaptogenesis. In addition, GABA_A receptor function is thought to contribute to normal postnatal maturation of neurons. Loss of postsynaptic GABA_A receptors in γ2-deficient neurons might therefore reflect a deficit in maturation of neurons due to the reduced channel function. Here, we have used the Cre-loxP strategy to examine the clustering function of the γ2 subunit at mature synapses. Deletion of the γ2 subunit in the third postnatal week resulted in loss of benzodiazepine-binding sites and parallel loss of punctate immunoreactivity for postsynaptic GABA_A receptors and gephyrin. Thus, the γ2 subunit contributes to postsynaptic localization of GABA_A receptors and gephyrin by a mechanism that is operant in mature neurons and not limited to immature neurons, most likely through interaction with proteins involved in trafficking of synaptic GABA_A receptors.