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通过区域特异性多巴胺动态在多个时间尺度上进行行为编码。

Behavioral encoding across timescales by region-specific dopamine dynamics.

机构信息

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Departments of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, 95616.

出版信息

Proc Natl Acad Sci U S A. 2023 Feb 14;120(7):e2215230120. doi: 10.1073/pnas.2215230120. Epub 2023 Feb 7.

Abstract

The dorsal (DS) and ventral striatum (VS) receive dopaminergic projections that control motor functions and reward-related behavior. It remains poorly understood how dopamine release dynamics across different temporal scales in these regions are coupled to behavioral outcomes. Here, we employ the dopamine sensor dLight1.3b together with multiregion fiber photometry and machine learning-based analysis to decode dopamine dynamics across the striatum during self-paced exploratory behavior in mice. Our data show a striking coordination of rapidly fluctuating signal in the DS, carrying information across dopamine levels, with a slower signal in the VS, consisting mainly of slow-paced transients. Importantly, these release dynamics correlated with discrete behavioral motifs, such as turns, running, and grooming on a subsecond-to-minute time scale. Disruption of dopamine dynamics with cocaine caused randomization of action selection sequencing and disturbance of DS-VS coordination. The data suggest that distinct dopamine dynamics of DS and VS jointly encode behavioral sequences during unconstrained activity with DS modulating the stringing together of actions and VS the signal to initiate and sustain the selected action.

摘要

背侧纹状体(DS)和腹侧纹状体(VS)接收多巴胺能投射,控制运动功能和与奖励相关的行为。多巴胺在这些区域的不同时间尺度上的释放动态如何与行为结果相关联,目前仍知之甚少。在这里,我们使用多巴胺传感器 dLight1.3b 结合多区域光纤光度法和基于机器学习的分析,在小鼠自主探索行为期间解码纹状体中的多巴胺动态。我们的数据显示,DS 中快速波动的信号与 VS 中的较慢信号之间存在惊人的协调,后者主要由慢节奏的瞬变组成。重要的是,这些释放动态与离散的行为模式相关,例如在亚秒到分钟的时间尺度上的转弯、跑步和梳理。可卡因对多巴胺动态的破坏导致动作选择序列的随机化和 DS-VS 协调的干扰。这些数据表明,DS 和 VS 的不同多巴胺动态共同编码非约束性活动期间的行为序列,DS 调节动作的串联,VS 则调节启动和维持所选动作的信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f442/9963838/8386a2dba60e/pnas.2215230120fig01.jpg

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