PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation.
PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation.
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DOI：
10.1038/ncomms13605
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发表时间：
2016-12-06
影响因子：
16.6
通讯作者：
Minamimoto, Takafumi
中科院分区：
文献类型：
--
作者：
Nagai, Yuji;Kikuchi, Erika;Lerchner, Walter;Inoue, Ken-ichi;Ji, Bin;Eldridge, Mark A. G.;Kaneko, Hiroyuki;Kimura, Yasuyuki;Oh-Nishi, Arata;Hori, Yukiko;Kato, Yoko;Hirabayashi, Toshiyuki;Fujimoto, Atsushi;Kumata, Katsushi;Zhang, Ming-Rong;Aoki, Ichio;Suhara, Tetsuya;Higuchi, Makoto;Takada, Masahiko;Richmond, Barry J.;Minamimoto, Takafumi
灵长类动物的吻内侧尾状核（rmCD）被认为有助于奖赏价值加工，但因果关系尚未建立。在这里，我们使用抑制性DREADD（设计师受体独家激活的设计师药物），以重复和非侵入性的猕猴mCD。我们将表达抑制性DREADD的腺相关病毒载体hM4Di双侧注射到rmCD中。为了可视化DREADD在体内的表达，我们开发了一种使用正电子发射断层扫描（PET）的非侵入性成像方法。PET成像提供了在实验期间成功的化学基因沉默的关键信息，在这种情况下，hM4Di表达的位置和水平，以及激动剂剂量和hM4Di受体占有率之间的关系。在这里，我们表明，通过激活hM4Di灭活双边rmCD产生一个显着的和可重复的损失的敏感性，在猴子的奖励价值。因此，rmCD参与了对奖励价值的正常判断。处理奖赏的价值被认为涉及吻内侧尾状核（rmCD），但在灵长类动物中缺乏因果关系的证明。在这里，作者使用化学遗传学和PET成像来表明，rmCD的失活导致奖励价值判断的损害。
The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET). PET imaging provides information critical for successful chemogenetic silencing during experiments, in this case the location and level of hM4Di expression, and the relationship between agonist dose and hM4Di receptor occupancy. Here we demonstrate that inactivating bilateral rmCD through activation of hM4Di produces a significant and reproducible loss of sensitivity to reward value in monkeys. Thus, the rmCD is involved in making normal judgments about the value of reward. Processing the value of reward is thought to involve the rostromedial caudate (rmCD), but a causal demonstration is lacking in primates. Here the authors use chemogenetics and PET imaging to show that inactivation of rmCD leads to impairments in reward value judgments.
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影响因子：
3.7
作者：
Oguchi M;Okajima M;Tanaka S;Koizumi M;Kikusui T;Ichihara N;Kato S;Kobayashi K;Sakagami M
通讯作者：
Sakagami M
影响因子：
5
作者：
Chen X;Choo H;Huang XP;Yang X;Stone O;Roth BL;Jin J
通讯作者：
Jin J
影响因子：
25
作者：
Eldridge MA;Lerchner W;Saunders RC;Kaneko H;Krausz KW;Gonzalez FJ;Ji B;Higuchi M;Minamimoto T;Richmond BJ
通讯作者：
Richmond BJ
DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
64.8
作者：
Tremblay, L;Schultz, W
通讯作者：
Schultz, W