SST interneurons facilitate dendritic calcium signaling via tonic activation of α5-GABA receptors

Brain activity is highly regulated by GABAergic activity, which can suppress neuronal excitability and synaptic integration. Tonic GABAergic conductances mediated by distinct receptor subtypes can also inhibit neural activity, although the consequences for dendritic calcium signaling are unclear. Here, we use 2-photon calcium imaging both ex vivo and in awake mice to show that α5-GABA A Rs mediate tonic currents in cortical pyramidal neurons that paradoxically enhance action potential-evoked dendritic calcium influx. Experimental and computational data indicate that the increased calcium influx arises via deinactivation of low-threshold voltage-gated channels. Tonic α5-mediated GABAergic currents and dendritic calcium signals are both enhanced by optogenetic activation of somatostatin-expressing interneurons (SST-INs). In addition, α5-mediated GABAergic facilitation of postsynaptic calcium signaling modulates the short-term plasticity of GABAergic transmission at SST-IN synapses. Our results demonstrate unexpected diversity in the function of both SST-INs and GABAergic signaling to influence dendritic activity and synaptic transmission in the cortex.