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bioRxiv · 10.1101/2021.01.29.428749

Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets

Mimura, K.·Nagai, Y.·Inoue, K.-i.·Matsumoto, J.·Hori, Y.·Sato, C.·Takada, M.·Suhara, T.·Higuchi, M.·Minamimoto, T.
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Abstract

To interrogate particular neuronal pathways in non-human 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 in three marmosets. Using multi-tracer positron emission tomography imaging, we detected DREADD expression in vivo, which was confirmed in nigrostriatal dopamine neurons by immunohisto-chemistry, and assessed activation of the substantia nigra and dopamine release 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 marmoset as a primate model for linking neuronal activity and natural behavior in various contexts.

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Mimura, K., Nagai, Y., Inoue, K.-i., Matsumoto, J., Hori, Y., Sato, C., Takada, M., Suhara, T., Higuchi, M., Minamimoto, T.. 2021-01-31. Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets. https://doi.org/10.1101/2021.01.29.428749

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