The GABAA Receptor β Subunit Is Required for Inhibitory Transmission

While the canonical assembly of a GABA(A) receptor contains two alpha subunits, two beta subunits, and a fifth subunit, it is unclear which variants of each subunit are necessary for native receptors. We used CRISPR/Cas9 to dissect the role of the GABA(A) receptor beta subunits in inhibitory transmission onto hippocampal CA1 pyramidal cells and found that deletion of all beta subunits 1, 2, and 3 completely eliminated inhibitory responses. In addition, only knockout of beta 3, alone or in combination with another beta subunit, impaired inhibitory synaptic transmission. We found that beta 3 knockout impairs inhibitory input from PV but not SOM expressing interneurons. Furthermore, expression of beta 3 alone on the background of the beta 1-3 subunit knockout was sufficient to restore synaptic and extrasynaptic inhibitory transmission. These findings reveal a crucial role for the beta 3 subunit in inhibitory transmission and identify a synapse-specific role of the beta 3 subunit in GABAergic synaptic transmission.