Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets

To interrogate particular neuronal pathways in nonhuman primates under natural and stress-free conditions, we applied designer receptors exclusively activated by designer drugs (DREADDs) technology to common marmosets. We injected adeno-associated virus vectors expressing the excitatory DREADD hM3Dq into the unilateral substantia nigra (SN) in fourmarmosets. Usingmulti-tracer positron emission tomography imaging, we detected DREADD expression in vivo, which was confirmed in nigrostriatal dopamine neurons by immunohistochemistry, as well as by assessed activation of the SN following agonist administration. The marmosets rotated in a contralateral direction relative to the activated side 30-90 min after consuming food containing the highly potent DREADD agonist deschloroclozapine (DCZ) but not on the following days without DCZ. These results indicate that non-invasive and reversible DREADD manipulation will extend the utility of marmosets as a primate model for linking neuronal activity and natural behavior in various contexts.

Automated summary

The researchers successfully introduced designer receptors activated by designer drugs (DREADDs) technology into common marmosets, allowing them to observe neuronal pathways under natural conditions. The results, confirmed through tracer imaging and immunohistochemistry, demonstrate the effectiveness of the experiment.