γ2 containing GABA_A receptors are the main GABA_ARs in most of the brain areas. We deleted the γ2 subunit gene from GABA_ARs selectively in the visual thalamus-the dorsal lateral geniculate nucleus (dLGN). The removal of the γ2 subunit from the dLGN reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and produced an absence of IPSCs in only a subset (50%) of relay neurons. The remaining slower IPSCs were both insensitive to diazepam and zinc indicating the absence of the γ2 subunit. Potentiation of IPSCs with DMCM suggests these IPSCs are γ1 subunit-containing.

In a seperate study, our collaborator showed that Sox14/Otx2-expressing precursor cells migrate from the dorsal midbrain to generate dLGN-INs. Abscence of Sox14 neurons reduced the total inhibition in dLGN relay neuron by 1/3, with remaining inhibition coming from reticular nucleus. Using optogenetics, we show that at increased firing rates, dLGN-INs generate a powerful form of tonic inhibition that regulates the gain of thalamic relay neurons through recruitment of extrasynaptic high-affinity GABA_A receptors.