Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets

Koki Mimura; Yuji Nagai; Ken-Ichi Inoue; Jumpei Matsumoto; Yukiko Hori; Chika Sato; Kei Kimura; Takashi Okauchi; Toshiyuki Hirabayashi; Hisao Nishijo; Noriaki Yahata; Masahiko Takada; Tetsuya Suhara; Makoto Higuchi; Takafumi Minamimoto

doi:10.1016/j.isci.2021.103066

Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets

iScience. 2021 Aug 30;24(9):103066. doi: 10.1016/j.isci.2021.103066. eCollection 2021 Sep 24.

Authors

Koki Mimura¹, Yuji Nagai¹, Ken-Ichi Inoue², Jumpei Matsumoto^{3

4}, Yukiko Hori¹, Chika Sato^{5

6}, Kei Kimura², Takashi Okauchi¹, Toshiyuki Hirabayashi¹, Hisao Nishijo^{3

4}, Noriaki Yahata^{5

6}, Masahiko Takada², Tetsuya Suhara¹, Makoto Higuchi¹, Takafumi Minamimoto¹

Affiliations

¹ Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555 Japan.
² Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
³ Department of System Emotional Science, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan.
⁴ Research Center for Idling Brain Science, University of Toyama, Toyama 930-8555, Japan.
⁵ Quantum Life Informatics Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555 Japan.
⁶ Applied MRI Research, Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555 Japan.

Abstract

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 four marmosets. Using multi-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.

Keywords: behavioral neuroscience; cellular neuroscience; molecular neuroscience.