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PET imaging-guided chemogenetic manipulation of primate neural circuits

https://repo.qst.go.jp/records/66119
https://repo.qst.go.jp/records/66119
e1b1642d-b847-4e30-b592-18e5276d30d9
Item type 会議発表用資料 / Presentation(1)
公開日 2017-02-15
タイトル
タイトル PET imaging-guided chemogenetic manipulation of primate neural circuits
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 南本, 敬史

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WEKO 650953

南本, 敬史

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南本 敬史

× 南本 敬史

WEKO 650954

en 南本 敬史

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内容記述タイプ Abstract
内容記述 Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying cognition and behavior. These tools should be especially useful in animals with larger brains because the designer drug, clozapine-N-oxide (CNO), can be administered systemically, thus providing a potential to control large and/or discontinuous regions of the brain. To interpret the behavioral outcome of experiments with the DREADD-CNO system in monkeys, it would be very useful to characterize the level and location of DREADD receptor expression, and the relationship of systemic CNO dose with the level of receptor activation while the experiments are ongoing. To measure these characteristics in vivo, we developed a non-invasive method for visualization of DREADDs using PET in rodents, and adapted the technique for the use in monkeys. With the DREADD-selective PET ligand, we can visualize the location and extent of expression, and measure DREADD receptor occupancy by CNO with a blocking protocol. Using this PET imaging-guided procedure, we demonstrated that chemogenetic inactivation of bilateral caudate nucleus produces a significant and reproducible loss of sensitivity to reward value in monkeys. The mechanism by which DREADDs work, and their potential for covering a large and diffuse population of neurons, as well as the capability of verifying DREADD expression by PET imaging before undertaking functional CNO activation experiments, ought to make this system an attractive tool for application to long-term behavioral studies, and potentially to clinical settings in the future.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 Seminar at NIDA
発表年月日
日付 2016-11-30
日付タイプ Issued
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