Department of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Commun. 2016 Dec 6;7:13605. doi: 10.1038/ncomms13605.
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.
灵长类动物的前内嗅尾状核（rmCD）被认为有助于奖励价值处理，但尚未建立因果关系。在这里，我们使用抑制性 DREADD（Designer Receptor Exclusively Activated by Designer Drug）来重复且非侵入性地使猕猴的 rmCD 失活。我们将表达抑制性 DREADD 的腺相关病毒载体 hM4Di 双侧注入 rmCD。为了在体内可视化 DREADD 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进行化学遗传沉默的关键信息，在这种情况下是 hM4Di 表达的位置和水平，以及激动剂剂量与 hM4Di 受体占有率之间的关系。在这里，我们证明通过激活 hM4Di 使双侧 rmCD 失活会导致猴子对奖励价值的敏感性显著且可重复地丧失。因此，rmCD 参与了对奖励价值的正常判断。
