Cerebellar and cerebro-cerebellar networks across the millisecond and circadian timescales

这项研究计划旨在了解大脑回路如何在毫秒级和全天功能上协调一致，以优化运动。参与运动的大脑区域，如小脑、基底节和大脑皮层，在运动前以零点几秒为基础相互作用，相互作用以改善信息交换，并微调选定的运动反应。许多结果表明，振荡活动在这一交流过程中发挥了作用。在证明了这些神经生理振荡受到昼夜节律的影响后，人们很有兴趣了解它们与功能任务的关系，以及干扰这些振荡如何影响表现。以小脑为起点，我们将研究这些脑区之间的相互作用在这两个时间尺度上是如何变化的。第一线的研究将集中在这些大脑区域在定时舔食任务中如何在声音或体感提示下相互作用。舔是啮齿类动物的一种自然节律行为。我们设计了一种“舔舔计”，它可以精确地测量舔舔行为，并用来描述这些大脑回路在运动开始之前是如何相互作用的。这一系列研究的结果将提供小脑局部回路以及长距离连接如何相互作用来支持间隔计时。第二条线的研究将涉及这些交流机制的昼夜节律性，重点是这些大脑系统可能如何相互作用。我们将测量在24小时一天的不同时期，小脑、纹状体和皮质在定时舔食任务中的相互作用。还将建立与分子钟的昼夜节律模式的关系。我们将研究这如何影响波活动的差异、信号之间的相干性，甚至是局部振荡对单位的影响。第三条研究路线涉及到通过小脑电刺激扰乱这些交流机制。通过Theta/Gamma节律刺激，我们将尝试调节区域间的通信，并影响定时舔食性能。这将为解释调制局部电路的振荡和更远距离的相互作用增加一个更多的因果角度。为了更好地理解结构间神经通信的基本原理，可以在这些较短期的目标上增加多条探究路线。通过将行为方法和日常方法结合起来，它解决了在时刻到时刻和昼夜尺度上的沟通模式。这一新的观点将有助于发展新的假设，通过不同结构的神经元群体进行神经交流。

This research program aims at understanding how brain circuits functionally coordinate together to optimize movement, at the millisecond level as well as throughout the day. Brain areas involved in movement, such as the cerebellum, basal ganglia, and the cerebral cortex, interact on a fraction-of-a-second basis, prior to movement, interact to improve the exchange of information, and fine-tune the chosen motor responses. Many results point to a role of oscillatory activity in this communication process. Having shown that these neurophysiological oscillations are affected by circadian rhythms, it is of high interest to see how they relate to functional tasks, and how perturbing these oscillations can affect performance. With the cerebellum as starting point, we will study how the interaction between these brain areas change on those two timescales. The first line of research will focus on how these brain areas interact in a timed licking task to a sound or somatosensory cue. Licking is a well described natural rhythmic behaviour in rodents. We have designed a "lickometer" that can precisely measure the licking behaviour and serve to describe how these brain circuits interact prior to movement onset. Results from this line of research will provide how local circuits in the cerebellum, as well as long-range connections, interact to support interval timing. The second line of research will touch on the circadian rhythmicity of these communication mechanisms, focusing on how these brain systems likely interact. We will measure how the cerebellum, striatum, and cortex interact in the timed licking task, at different periods of the 24-hr day. The relation with the circadian patterns of the molecular clocks will be established as well. We will study how this affects the differences in wave activity, in the coherence between signals, or even how the units are influenced by the local oscillations. The third line of research touches on perturbing these communication mechanisms, via cerebellar electrical stimulation. With theta/gamma rhythmic stimulation, we will attempt to modulate inter-area communication and affect timed licking performance. This will add a more causal angle to the interpretation of oscillations modulating local circuits and more distant interactions. Multiple lines of inquiry can be added to these shorter term aims, all to better understand basic principles of inter-structure neural communication. By combining the behavioural and daily approaches, it addresses the modes of communication on the moment-to-moment and circadian scales. This new perspective will serve to develop new hypotheses on neural communication by populations of neurons across different structures.