霊長類脳でのドーパミン蛍光計測に成功~ドーパミンの機能解明へ大きく前進~

ad

2025-03-14 京都大学

京都大学の研究グループは、霊長類の脳内でドーパミンを蛍光センサーを用いて計測することに世界で初めて成功しました。ドーパミンは中脳の神経細胞から大脳基底核の線条体に放出され、適切な行動の獲得に重要な役割を果たします。従来の手法では霊長類の脳内でのドーパミン神経伝達を高精度に計測することが困難でしたが、今回の技術により、サルの線条体で放出されるドーパミンを高感度かつ迅速に検出することが可能となりました。これにより、サルが報酬を予測している際に、価値判断に関わるドーパミン信号が線条体に入力していることが明らかになりました。この成果は、ドーパミンが関与する神経変性疾患の病態解明や新たな治療法の開発に貢献することが期待されます。

<関連情報>

霊長類線条体へのドーパミンシグナル伝達の蛍光検出と刺激と報酬の関連性 Fluorescence detection of dopamine signaling to the primate striatum in relation to stimulus–reward associations

Gaoge Yan, Hidetoshi Amita, Satoshi Nonomura, +2 , and Masahiko Takada
Proceedings of the National Academy of Sciences  Published:March 13, 2025
DOI:https://doi.org/10.1073/pnas.2426861122

霊長類脳でのドーパミン蛍光計測に成功~ドーパミンの機能解明へ大きく前進~

Significance

Reward-anticipatory behavior following a reward-predicting stimulus is achieved through Pavlovian conditioning. Dopamine (DA) released within the striatum, the main input station of the basal ganglia, plays a key role in this behavior. However, it remains unclear what type of DA signal is conveyed to the striatum in relation to stimulus-reward associations. To detect DA transients in the anterior striatal sectors responsible for the stimulus-reward associations, we applied fiber photometry with a fluorescent DA sensor to monkeys being engaged in a Pavlovian conditioning task. Our study demonstrates that this technique is useful to capture the DA transients in brain structures of the task-performing monkeys, and that the DA transients vary depending on the striatal territories.

Abstract

Dopamine (DA) signals to the striatum play critical roles in shaping and sustaining stimulus-reward associations. In primates, however, the dynamics of the DA signals remain unknown since conventional methods are not necessarily appropriate in terms of the spatiotemporal resolution or chemical specificity sufficient for detecting the DA signals. In our study, fiber photometry with a fluorescent DA sensor was employed to identify reward-related DA transients in the monkey striatum. This technique, which directly monitors local DA release, reveals a reward prediction error signal in the anterior putamen originating from midbrain DA neurons. Further, DA transients in the head of the caudate nucleus exhibit a value-based response to reward-predicting stimuli. These signals have been found to arise from two separate groups of DA neurons in the substantia nigra pars compacta. The present results demonstrate that fluorescence DA monitoring is applicable to detect DA signals in the primate striatum for investigating their roles.

医療・健康
ad
ad
Follow
ad
タイトルとURLをコピーしました