CRCNS: Network mechanisms of the learning and encoding of timed motor responses

大脑是一个内在的动态系统，它在强大的选择压力下进化，允许动物 与环境实时互动，并预测和准备未来的事件。由于这些原因， 理解神经动力学，以及大脑如何告诉和编码时间是理解的基础。 大脑功能神经动力学和时间对大脑功能的重要性强调了 这些技术允许收集和分析大规模并行的单个神经元记录， 行为动物的多重结构。这个项目将联合收割机结合新颖的电生理学，行为学， 分析和计算方法，以逆向工程的神经回路的学习和时间。 第一个目标是将联合收割机大规模神经记录与计算方法相结合，以确定 时间在纹状体和前额叶皮层中表现，这两个相互作用的大脑区域密切相关。 与时间处理有关我们将具体研究时间编码是否依赖于绝对， 相对的或刺激特异性的编码机制。记录将在清醒、头部固定的小鼠中进行 在经典的跟踪奖励条件反射任务中，两个线索以不同的延迟预测奖励 期当动物学会了线索-奖励的关联，它们会进行强烈的预期性舔， 在奖励呈现之前;此外，这种行为的时机取决于线索奖励 延迟时间第二个目标是结合联合收割机电生理学和光遗传学，以确定是否存在时间 纹状体和前额叶皮层中的编码被暂时中断的网络活动扰乱。的 假设是，如果定时电路的动态被扰动，则随后的活动模式将被 不可逆地改变，从而降低定时行为反应的准确性或精确性。第三个目标是 开发一种基于递归神经网络模型的新型计算框架， 基于“现在”模式的神经集合活动的“未来”模式。这项工作的最终目标是 集成高度创新脑电生理学和计算方法的逆向工程 在纹状体和前额叶皮层的数百个神经元网络的水平上的电路功能。 相关性（参见说明）： 学习产生适当的时间动作是行为和破坏的许多方面的基础 这一过程背后的大脑回路的变化与许多神经和精神疾病有关。这 该项目将开发一种综合方法来研究定时运动行为的机制， 结合来自多个大脑区域的大规模神经记录和神经元的计算建模， 网络.

The brain is an inherently dynamic system, it evolved under strong selective pressures to allow animals to interact with the environment in real-time, and predict and prepare for future events. For these reasons, understanding neural dynamics, and how the brain tells and encodes time is fundamental to understanding brain function. The importance of neural dynamics and timing to brain function emphasizes the need for techniques that allow for the collection and analysis of massively parallel single neuron recordings across multiple structures in behaving animals. This project will combine novel electrophysiological, behavioral, analytical and computational methods to reverse engineer the neural circuits underlying learning and timing. The first aim is to combine large-scale neural recordings with computational approaches to determine how time is represented in the striatum and prefrontal cortex, two interacting brain areas that are closely implicated in temporal processing. We will specifically examine whether encoding of time relies on absolute, relative, or stimulus-specific coding mechanisms. Recordings will be carried out in awake, head-fixed mice trained on a classical trace reward conditioning task in which two cues predict reward with a different delay period. When animals learn the cue-reward association, they engage in robust anticipatory licking that precedes the reward presentation; moreover, the timing of this behavior is dependent on the cue-reward delay time. The second aim is to combine electrophysiology and optogenetics to determine if temporal coding in the striatum and prefrontal cortex is perturbed by transiently disrupting network activity. The hypothesis is that if dynamics of the timing circuits are perturbed then the ensuing activity patterns will be irreversibly altered, thus reducing the accuracy or precision of timed behavioral responses. The third aim is to develop a novel computational framework based on recurrent neural networks models that can predict "future" patterns of neural ensemble activity based on "present" patterns. The ultimate goal of this work is to integrate highly innovative electrophysiological and computational methods for reverse engineering brain circuit function at the level of networks of hundreds of neurons in the striatum and prefrontal cortex. RELEVANCE (See instructions): Learning to produce appropriately timed actions is fundamental to many aspects of behavior, and disruption of the brain circuits underlying this process is implicated in many neurological and psychiatric disorders. This project will develop an integrated approach to studying the mechanisms of timed motor behavior by combining large-scale neural recordings from multiple brain areas and computational modeling of neural networks.