RGS2 Determines Short-Term Synaptic Plasticity in Hippocampal Neurons by Regulating G_i/o- Mediated Inhibition of Presynaptic Ca²⁺ Channels

RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates G_i/o as well as G_q-coupled receptor pathways. RGS2 modulates anxiety, aggression, and blood pressure in mice, suggesting that RGS2 regulates synaptic circuits underlying animal physiology and behavior. How RGS2 in brain influences synaptic activity is unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal neurons by comparing electrophysiological recordings from RGS2 knockout and wild-type mice. Our study provides a general mechanism of the action of the RGS family containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by downregulating the G_i/o-mediated presynaptic Ca²⁺ channel inhibition and therefore provides an explanation of how regulation of RGS2 expression can modulate the function of neuronal circuits underlying behavior.