Ionic Mechanisms Involved in β3‐Adrenoceptor‐Mediated Augmentation of GABAergic Transmission Onto Pyramidal Neurons in Prefrontal Cortex

ABSTRACT Activation of the brain‐penetrant beta3‐adrenergic receptor (Adrb3) is implicated in the treatment of depressive disorders. Enhancing GABAergic inputs from interneurons onto pyramidal cells of prefrontal cortex (PFC) represents a strategy for antidepressant therapies. Here, we probed the effects of the activation of Adrb3 on GABAergic transmission onto pyramidal neurons in the PFC using in vitro electrophysiology. We found that Adrb3 agonist SR58611A increased both the frequency and the amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T‐type voltage‐gated Ca 2+ channel (T‐type VGCC) contributed to SR58611A‐enhanced mIPSC frequency. We also found that SR58611A facilitated GABA release probability and the number of releasable vesicles through interaction with T‐type VGCC. SR58611A depolarized somatostatin (Sst) interneurons with no effects on the firing rate of action potential of Sst interneurons. SR58611A‐induced depolarization of Sst interneurons and enhancement of mIPSC frequency required inward rectifier K + channel (Kir). Our results suggest that Kir and T‐type VGCC in Sst interneurons participate in SR58611A‐induced increase in GABA release in PFC. image