记忆诱导序列眼动的皮层调控机制

Sequences of information or sequences of actions are used in various everyday tasks. They range from the relatively simple and practiced, such as brushing teeth, to the more complex and infrequent such as playing piano. Deficits in sequential multistep tasks are pervasive across many neurological and psychiatric disorders, and many patients cannot function normally in daily life. Thus, a better understanding of how we perform sequences of tasks and the underlying neural circuitry would make great strides towards helping large populations of people with deficits in these functions. In addition, we would contribute to our understanding of a fundamental, yet complex, daily behavior. The saccadic eye movement provides an excellent model for investigating sequential motor learning since not only the input is highly controllable and easily specified, but also the output is highly constrained and easy to measure with high precision. We will perform behavioral and electrophysiological experiments with trained primates to search neural correlates for sequential saccade. Then we will test for direct link between neuronal activity and sequential eye movements by manipulate neural activity using micro-stimulation and reversible chemical inactivation. Cortical areas FEF, SEF and LIP will be investigated because these areas have previously been implicated in saccade planning and execution. Finally, we will try optogenetics approaches to directly observe and manipulate the neural circuitry in sequential task. This series of studies will not only extend our knowledge regarding the sequence learning, but also bridge the gap between cell-type specific analyses of individual neurons and sequence saccade. Besides, it also provides scientific basis for the practical application of artificial intelligence, development of new educational programs, clinical diagnosis and treatment technologies.

有序地产生有组织的行为，也称序列运动，对人们的日常生活和学习至关重要，如我们说话、书写、骑车、弹琴、打球等，其流畅的完成都基于序列运动学习。在一些功能性脑病患者中，感知和学习序列的能力出现受损，给生活带来了极大的不便，但目前对于序列运动学习的神经机制尚不清楚。本项目以序列眼动为模型，在猕猴执行任务的同时，对眼动相关脑区的神经元活动进行电生理记录，并结合微电流刺激、可逆药物失活、光遗传技术来探索特定脑区、特定细胞类型、特定的神经元回路与记忆诱导的序列眼动行为之间的功能性联系。这些研究结果不仅可以清晰地了解序列眼动这种容易观测到的外显行为的内在机制，还为研发人工智能、发展新的教育方案等实际应用提供科学依据，同时也为序列学习和执行能力减弱或丧失的病人提供更好更有效的治疗理论基础。

本项目主要以序列眼动为行为范式对序列运动学习的神经进行探索：首先对猕猴进行左-左-右-右的序列眼动任务训练，待猕猴学会序列眼动行为后，在执行任务的同时对眼动相关脑区（额叶眼动区FEF、后顶叶皮层的顶内沟外侧区LIP、辅助区眼动中枢SEF等）的单个/多个神经元活动以及局部场电位进行记录，并结合微电流刺激、可逆药物失活、光遗传技术来探索不同脑区、不同神经元回路与序列眼动行为之间的功能性联系。主要的发现是FEF、LIP和SEF等脑区都动态编码了序列眼动的计划和执行。进一步微电流刺激改变序列执行过程中FEF神经元的敏感性但不改变序列执行的结构，提示序列眼动的执行是不由单个脑区决定，而可能由多个脑区构成的分层网络协同进行，FEF很可能位于序列执行网络的较低层级的控制水平上。