Cellular mechanisms and efficacy of hM4Di-dependent chemogenetic silencing in the developing hippocampus
Chemogenetic techniques have broadened our understanding of how early activity shapes developing brain circuits. A widely used chemogenetic actuator is hM4Di, which employs Gi/o-protein signaling for neuronal inhibition. However, its single-cellular mechanisms and efficacy in neurons with immature Gi/o signaling are elusive. Here, we investigate the applicability of transgenically expressed hM4Di for silencing pyramidal cells in the hippocampus of neonatal mice. Electrophysiological recordings from CA1 pyramidal cells demonstrate that hM4Di does not mediate hyperpolarization or shunting and, i