Specialized coding of sensory, motor and cognitive variables in VTA dopamine neurons
Specialized coding of sensory, motor and cognitive variables in VTA dopamine neurons
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DOI：
10.1038/s41586-019-1261-9
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发表时间：
2019-06-27
期刊：
影响因子：
64.8
通讯作者：
Witten, Ilana B.
中科院分区：
文献类型：
--
作者：
Engelhard, Ben;Finkelstein, Joel;Witten, Ilana B.
越来越多的人认识到，中脑中的多巴胺神经元不仅对奖励（1）和奖励预测线索（1，2）做出反应，而且还对其他变量做出反应，如奖励的距离3，运动（4-9）和行为选择（10，11）。一个重要的问题是，对这些不同变量的反应是如何在多巴胺神经元群体中组织起来的。单个多巴胺神经元是否能多重化几个变量，或者是否有专门编码特定行为变量的神经元子集，目前尚不清楚。这个基本问题一直很难解决，因为记录从大人口的个别多巴胺神经元还没有进行的行为任务具有足够的复杂性，以检查这些不同的变量同时进行。在这里，为了解决这一差距，我们使用双光子钙成像通过植入透镜，以记录超过300多巴胺神经元的活动，从腹侧被盖区的小鼠中脑在一个复杂的决策任务。当小鼠在虚拟现实环境中导航时，多巴胺神经元编码了一系列感觉，运动和认知变量。这些反应在功能上是聚集的，这样神经元的亚群除了编码奖励之外，还传递了关于行为变量子集的信息。这些功能簇在空间上是有组织的，相邻的神经元更可能是同一簇的一部分。再加上多巴胺神经元及其投射之间的拓扑结构，这种专门化和解剖组织可能有助于下游回路正确解释多巴胺神经元传输的广泛信号。
There is increased appreciation that dopamine neurons in the midbrain respond not only to reward(1) and reward-predicting cues(1,2), but also to other variables such as the distance to reward3, movements(4-9) and behavioural choices(10,11). An important question is how the responses to these diverse variables are organized across the population of dopamine neurons. Whether individual dopamine neurons multiplex several variables, or whether there are subsets of neurons that are specialized in encoding specific behavioural variables remains unclear. This fundamental question has been difficult to resolve because recordings from large populations of individual dopamine neurons have not been performed in a behavioural task with sufficient complexity to examine these diverse variables simultaneously. Here, to address this gap, we used two-photon calcium imaging through an implanted lens to record the activity of more than 300 dopamine neurons from the ventral tegmental area of the mouse midbrain during a complex decision-making task. As mice navigated in a virtual-reality environment, dopamine neurons encoded an array of sensory, motor and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioural variables, in addition to encoding reward. These functional clusters were spatially organized, with neighbouring neurons more likely to be part of the same cluster. Together with the topography between dopamine neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by dopamine neurons.