Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets

To interrogate particular neuronal pathways in nonhuman primates under naturaland stress-free conditions, we applied designer receptors exclusively activatedby designer drugs (DREADDs) technology to common marmosets. We injectedadeno-associated virus vectors expressing the excitatory DREADD hM3Dq intothe unilateral substantia nigra (SN) in fourmarmosets. Usingmulti-tracer positronemission tomography imaging, we detected DREADD expression in vivo, whichwas confirmed in nigrostriatal dopamine neurons by immunohistochemistry, aswell as by assessed activation of the SN following agonist administration. Themarmosets rotated in a contralateral direction relative to the activated side30–90 min after consuming food containing the highly potent DREADD agonistdeschloroclozapine (DCZ) but not on the following days without DCZ. These resultsindicate that non-invasive and reversible DREADD manipulation will extendthe utility of marmosets as a primate model for linking neuronal activity and naturalbehavior in various contexts