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hM4Di AAV is a research-stage chemogenetic tool belonging to the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) platform, originally developed by the Roth laboratory at the University of North Carolina. It consists of an adeno-associated virus (AAV) vector encoding hM4Di, an engineered inhibitory Gi-coupled human muscarinic receptor. This receptor is designed to be selectively activated by otherwise pharmacologically inert ligands, such as clozapine-N-oxide (CNO) or compound 21 (C21). Upon AAV-mediated delivery and expression in specific neuronal populations, the administration of the designer ligand induces Gi-protein signaling, leading to neuronal hyperpolarization and suppression of activity. It is widely utilized as a preclinical neuroscience research tool for the reversible inhibition of neurons to study their functional roles in various physiological and pathological processes, including stress responses, substance use disorders, and epilepsy.
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