Synaptic Gα12/13 signaling establishes hippocampal PV inhibitory circuits

Combinatorial networks of cell adhesion molecules and cell surface receptors drive fundamental aspects of neural circuit establishment and function. However, the intracellular signals orchestrated by these cell surface complexes remain less understood. Here, we report that the Gα12/13 pathway lies downstream of several GPCRs with critical synaptic functions. Impairment of the Gα12/13 pathway in postnatal hippocampal neurons diminishes inhibitory inputs without altering neuronal morphology or excitatory transmission. Gα12/13 signaling in hippocampal CA1 neurons in vivo selectively regulates PV interneuron synaptic connectivity, supporting an inhibitory synapse subtype-specific function of this pathway. Our studies establish Gα12/13 as a signaling node that shapes inhibitory hippocampal circuitry.