Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Nature. 2023 Feb;614(7946):108-117. doi: 10.1038/s41586-022-05611-2. Epub 2023 Jan 18.
Spontaneous animal behaviour is built from action modules that are concatenated by the brain into sequences. However, the neural mechanisms that guide the composition of naturalistic, self-motivated behaviour remain unknown. Here we show that dopamine systematically fluctuates in the dorsolateral striatum (DLS) as mice spontaneously express sub-second behavioural modules, despite the absence of task structure, sensory cues or exogenous reward. Photometric recordings and calibrated closed-loop optogenetic manipulations during open field behaviour demonstrate that DLS dopamine fluctuations increase sequence variation over seconds, reinforce the use of associated behavioural modules over minutes, and modulate the vigour with which modules are expressed, without directly influencing movement initiation or moment-to-moment kinematics. Although the reinforcing effects of optogenetic DLS dopamine manipulations vary across behavioural modules and individual mice, these differences are well predicted by observed variation in the relationships between endogenous dopamine and module use. Consistent with the possibility that DLS dopamine fluctuations act as a teaching signal, mice build sequences during exploration as if to maximize dopamine. Together, these findings suggest a model in which the same circuits and computations that govern action choices in structured tasks have a key role in sculpting the content of unconstrained, high-dimensional, spontaneous behaviour.
自发性动物行为是由大脑将动作模块串联而成的。然而，引导自然动机行为组成的神经机制仍然未知。在这里，我们表明，尽管没有任务结构、感官提示或外源性奖励，多巴胺在背外侧纹状体（DLS）中会系统地波动，因为老鼠会自发地表达亚秒级的行为模块。在开放场行为期间进行的光度记录和校准的闭环光遗传学操作表明，DLS 多巴胺波动会在数秒内增加序列变化，在数分钟内增强与行为模块相关的使用，调节模块表达的活力，而不会直接影响运动启动或瞬间运动学。尽管光遗传学 DLS 多巴胺操作的强化作用因行为模块和个体老鼠而异，但这些差异与内源性多巴胺与模块使用之间的关系的观察到的变化很好地预测。与 DLS 多巴胺波动作为教学信号的可能性一致，老鼠在探索期间构建序列，好像是为了最大化多巴胺。总之，这些发现表明了一个模型，即控制结构化任务中动作选择的相同电路和计算在塑造无约束、高维、自发行为的内容方面具有关键作用。
