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- Title
Multimodal Imaging for Validation and Optimization of Ion Channel-Based Chemogenetics in Nonhuman Primates.
- Authors
Yuki Hori; Yuji Nagai; Yukiko Hori; Kei Oyama; Koki Mimura; Toshiyuki Hirabayashi; Ken-ichi Inoue; Masayuki Fujinaga; Ming-Rong Zhang; Masahiko Takada; Makoto Higuchi; Takafumi Minamimoto
- Abstract
Chemogenetic tools provide an opportunity to manipulate neuronal activity and behavior selectively and repeatedly in nonhuman primates (NHPs) with minimal invasiveness. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are one example that is based on mutated muscarinic acetylcholine receptors. Another channel-based chemogenetic system available for neuronal modulation in NHPs uses pharmacologically selective actuator modules (PSAMs), which are selectively activated by pharmacologically selective effector molecules (PSEMs). To facilitate the use of the PSAM/PSEM system, the selection and dosage of PSEMs should be validated and optimized for NHPs. To this end, we used a multimodal imaging approach. We virally expressed excitatory PSAM (PSAM4-5HT3) in the striatum and the primary motor cortex (M1) of two male macaque monkeys, and visualized its location through positron emission tomography (PET) with the reporter ligand [18F]ASEM. Chemogenetic excitability of neurons triggered by two PSEMs (uPSEM817 and uPSEM792) was evaluated using [18F]fluorodeoxyglucose-PET imaging, with uPSEM817 being more efficient than uPSEM792. Pharmacological magnetic resonance imaging (phMRI) showed that increased brain activity in the PSAM4-expressing region began ;13min after uPSEM817 administration and continued for at least 60 min. Our multimodal imaging data provide valuable information regarding the manipulation of neuronal activity using the PSAM/PSEM system in NHPs, facilitating future applications.
- Subjects
CHOLINERGIC receptors; MUSCARINIC acetylcholine receptors; PRIMATES; POSITRON emission tomography; MAGNETIC resonance imaging; DESIGNER drugs
- Publication
Journal of Neuroscience, 2023, Vol 43, Issue 39, p6619
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0625-23.2023