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

该研究项目旨在了解大脑回路如何在毫秒级以及全天的水平上协调功能以优化运动。参与运动的大脑区域，如小脑、基底神经节和大脑皮层，在运动前以几分之一秒为基础相互作用，相互作用以改善信息交换，并微调所选择的运动反应。许多结果指出振荡活动在这一交流过程中的作用。在证明了这些神经生理振荡受昼夜节律影响之后，研究它们与功能性任务的关系以及干扰这些振荡如何影响表现是非常有趣的。以小脑为起点，我们将研究这些大脑区域之间的相互作用在这两个时间尺度上是如何变化的。研究的第一步将集中在这些大脑区域如何在定时舔舐任务中与声音或体感线索相互作用。舔是啮齿类动物的一种被很好地描述的自然节律行为。我们设计了一种“舔舐计”，可以精确测量舔舐行为，并用于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的局部回路以及远程连接如何相互作用以支持间隔时间。第二项研究将涉及这些通信机制的昼夜节律性，重点关注这些大脑系统如何可能相互作用。我们将测量小脑、纹状体和皮层在24小时内的不同时段如何在定时舔舐任务中相互作用。与分子钟的昼夜节律模式的关系也将建立。我们将研究这如何影响波活动的差异，信号之间的相干性，甚至单元如何受到局部振荡的影响。第三条研究路线涉及通过小脑电刺激干扰这些通讯机制。通过有节奏的刺激，我们将尝试调节区域间的交流并影响定时舔舐的表现。这将为调制局部电路和更远距离相互作用的振荡的解释增加更多的因果角度。为了更好地理解结构间神经通讯的基本原理，可以在这些短期目标中增加多个调查线。通过结合行为和日常方法，它解决了每时每刻和昼夜节律尺度上的交流模式。这一新的观点将有助于对不同结构的神经元群体的神经通信提出新的假设。

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.