Dopamine and glutamate regulate striatal acetylcholine in decision-making.
Dopamine and glutamate regulate striatal acetylcholine in decision-making.
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DOI：
10.1038/s41586-023-06492-9
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发表时间：
2023-09
期刊：
影响因子：
64.8
通讯作者：
Sabatini, Bernardo L.
中科院分区：
文献类型：
--
作者：
Chantranupong, Lynne;Beron, Celia C.;Zimmer, Joshua A.;Wen, Michelle J.;Wang, Wengang;Sabatini, Bernardo L.
纹状体多巴胺和乙酰胆碱对于选择和加强运动动作和决策至关重要。体外研究揭示了纹状体内回路，其中由胆碱能中间神经元（CINs）释放的乙酰胆碱驱动多巴胺的释放，而多巴胺反过来通过多巴胺D2受体（D2Rs）抑制CINs的活性。这个回路是否以及如何在体内促进纹状体功能在很大程度上是未知的。在这里，为了确定这个回路在生命系统中的作用，我们监测了执行奖励决策任务的小鼠腹外侧纹状体中的乙酰胆碱和多巴胺信号。我们确定，多巴胺和乙酰胆碱表现出多相和神经元相关的瞬态调制的决策历史和奖励的结果。多巴胺动力学和奖赏编码不需要通过CIN释放乙酰胆碱。然而，多巴胺以D2R依赖的方式抑制乙酰胆碱瞬变，这种调节的丧失会损害决策。为了确定其他纹状体输入如何塑造乙酰胆碱信号，我们评估了皮质和丘脑投射的贡献，发现乙酰胆碱释放需要两个来源的谷氨酸释放。总之，我们揭示了决策过程中多巴胺和乙酰胆碱之间的动态关系，并揭示了CIN调节的多种模式。这些发现加深了我们对决策和行为的神经化学基础的理解。小鼠实验提供了对腹外侧纹状体中多巴胺和乙酰胆碱之间动态关系的深入了解，以及这种信号回路如何影响决策和行为。
Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour. Experiments in mice provide insight into the dynamic relationship between dopamine and acetylcholine in the ventrolateral striatum and how this signalling circuit affects decision-making and behaviour.
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影响因子：
16.2
作者：
Chuhma N;Mingote S;Moore H;Rayport S
通讯作者：
Rayport S
影响因子：
16.2
作者：
Lee J;Finkelstein J;Choi JY;Witten IB
通讯作者：
Witten IB
DOI：
10.1073/pnas.81.15.4998
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KIMURA, M;RAJKOWSKI, J;EVARTS, E
通讯作者：
EVARTS, E
影响因子：
64.8
作者：
Lee SJ;Lodder B;Chen Y;Patriarchi T;Tian L;Sabatini BL
通讯作者：
Sabatini BL
影响因子：
16.6
作者：
Fisher, Simon D.;Robertson, Paul B.;Reynolds, John N. J.
通讯作者：
Reynolds, John N. J.