基于努力的行为抉择：前额叶神经元编码及前脑环路调控

Decision making strategy and its results are subject to efforts. Studies show that prefrontal cortex（PFC）plays a key role in decision making, and forebrain circuits are involved in effort-related functions. However, little is known about the neural mechanisms of forebrain circuits in regulation of effort-based decision making. In this project, we plan to record neuron spike activity in medial prefrontal cortex (mPFC) and interfere with forebrain circuits simultaneously so as to clarify forebrain circuit mechanisms in regulation of effort-based decision making. Specific approaches are included: 1) We will train rats to perform an effort-based decision making task, record the activity of mPFC neurons with the multiple channel array recording technology, and decode the prefrontal decision making algorithms by a new mathematical modeling. 2) To clarify the role of forebrain circuit in mediation of prefrontal decision making algorithms, we will analyze the dynamic changes of mPFC neuronal firing patterns while the rats' task is afftected by interferences with forebrain circuits, including pharmacologically inactivate of nucleus accumbens, ventral tegmental area or dorsomedial hypothalamic nucleus, and bidirectionally adjust the activities of mediodorsal thalamus nucleus or ventral tegmental areas using optogenetic method.

行为抉择的策略和结果受行为努力程度的影响。研究表明，前额叶皮层（PFC）在基于努力的行为抉择中起核心作用，而行为努力付出的过程需要前脑环路（伏隔核、腹侧被盖区、丘脑背内侧核）的参与。然而，前脑环路如何参与调控基于努力的行为抉择，尚不清楚。本项目拟通过人为干预的方式改变大鼠前脑环路功能，观察对内侧前额叶皮层（mPFC）神经元活动的影响，以期阐明前脑环路调控基于努力的行为抉择的神经元机制。具体研究内容：1）训练大鼠执行基于努力的行为抉择任务，采用多通道记录技术追踪mPFC任务相关神经元的活动，通过数学建模解析mPFC行为抉择的计算模式；2）采用药理学方法失活伏隔核、丘脑背内侧核或腹侧被盖区，或运用光遗传学手段,调节丘脑背内侧核或腹侧被盖区的活动，观察mPFC抉择相关神经元活动，分析前脑环路对mPFC抉择计算模式的调控机制。

行为抉择的策略和结果受行为努力程度的影响。研究表明，前额叶皮层（PFC）在基于努力的行为抉择中起核心作用，而行为努力付出的过程需要前脑环路的丘脑背内侧核的参与。本项目，我们训练大鼠执行基于努力的行为抉择任务，采用多通道记录技术追踪内侧前额叶皮层任务相关神经元的活动，通过数学建模解析内侧前额叶皮层行为抉择的计算模式；我们采用药理学方法失活伏丘脑背内侧核，和运用光遗传学手段调节丘脑背内侧核活动，发现内侧前额叶皮层抉择相关神经元活动和大鼠的行为抉择操作都受到双向调控。通过这种人为干预的方式改变大鼠前脑环路功能，观察对内侧前额叶皮层神经元活动的影响，我们基本阐明了前脑环路调控基于努力的行为抉择的神经元机制。