初级听觉皮层对听觉预测运动行为的调节及机制

The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior, however, the conditions of neural and mental diseases are generally associated with the disorder of auditory anticipatory behavior. Neocortical circuits for immediate processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. In our previous study, we found neuronal ensembles in layers 2/3 that were activated in relationship to anticipated sound events following rhythmic stimulation. Therefore, in present project we plan to use in vivo cellular imaging and fiber photometry to record mouse primary auditory cortex to elucidate its role in processing anticipated stimulation. And then we will investigate the relationship between the neuronal activities and the occurrence of anticipatory motor responses during an auditory associative learning task. Moreover, optogenetic technique will be applied to reveal the role of neuronal activities in producing the behavior. Based on these, we may be able to clarify the mechanisms of primary sensory cortical circuit for coding predictive information and transforming it into anticipatory behavior.

大脑基于近期感觉经验去预测将来事件的能力对于主导动物的行为是极其重要的，而在神经及精神类疾病条件下，常常伴有感觉预测运动行为异常。大脑皮层环路对即时的感觉刺激处理已经被广泛地研究，但是对于即将出现的感觉刺激的预测的贡献仍然是缺乏理解的。在前期工作中，我们发现在听觉皮层第2/3层的部分神经元在经过节律性的刺激后可以反应预测声音的事件。为此，在本项目中我们计划先采用在体细胞成像和光纤记录技术去记录小鼠初级听觉皮层神经元活动从而理解它们处理预测刺激的作用。然后在一个听觉学习任务中，进一步观察神经活动与预期出现的运动反应的相关性，并采用光遗传学技术揭示这种神经活动对产生运动行为的影响，从而在细胞分辨率水平上阐明初级感觉皮层环路对编码预测信息和转换为预期行为的重要性。

基于过去学习的经验，预测即将到来的事件，是动物一项非常重要的基本能力。这种预测能力对动物的决策和认知等高级功能都有重要影响。我们利用双光子显微成像技术发现了小鼠初级听皮层的部分神经元在连续多次时间间隔相同的声音刺激后，会产生多一次的响应，我们称之为回波反应。这个回波反应就是神经元基于前面的刺激对即将发生的刺激进行的预测。与此同时，我们建立了小鼠感知运动行为学，训练小鼠听声音舔水。我们发现给小鼠连续多次时间间隔相同的声音刺激后，小鼠会产生回波反应舔水，这个舔水动作与听皮层神经元的回波反应高度相关，而且不依赖于听觉丘脑的信息传递。光遗传学抑制听皮层可以有效的抑制小鼠的回波反应舔水。光遗传学兴奋训练后的小鼠可以直接引起舔水反应和回波反应舔水动作。