Behavioral state modulation of sensorimotor processing in cerebellar microcircuits

项目摘要 行为和大脑状态的每时每刻的波动已经被证明对 人类和实验动物的感知和行为。行为反应的可变性 由这些波动引起的波动具有真实的世界效应，因为它们可以引起个体的反应， 在高风险和高要求的情况下，如驾驶汽车或为病人做手术，在 此外，如果不考虑，波动可能是两种临床治疗中变异性增加的来源 和系统神经科学研究，降低了治疗的有效性和鲁棒性， 试验结果到目前为止，在理解状态对神经处理的影响方面取得的大部分进展都是 来自于感觉回路的实验。但是知道状态如何影响感觉处理还不足以 理解它是如何影响行为的，因为神经回路有许多额外的下游阶段， 在最终电机输出之前进行处理。这个项目的目标是检查状态对感官和感官的影响。 和运动系统来实现同样的行为。这将通过利用感觉运动任务来完成 延迟眨眼条件反射（delay eyeblink conditioning，dEBC），其中感觉系统和运动系统之间的大部分处理发生 在一个单一的大脑区域（小脑）。这些实验将首先涉及开发新的定量 基于心理物理学的方法来测试状态对dEBC的影响。两种不同的行为状态 将被检查-运动和唤醒-实验的目的是梳理除了相对的影响 这两个州的数据然后，实验将使用大规模成像和电生理学来测试， 以及小脑的输入（感觉）和输出（运动）神经元如何受到状态的影响。的结果 这些实验将首次展示整个神经系统和行为是如何动态地 在亚秒到秒的时间尺度上由状态调制。更好地理解国家对 行为表现背后的神经加工将为优化实验提供关键信息 设计和治疗。

PROJECT SUMMARY Moment-to-moment fluctuations in behavioral and brain states have been shown to have profound effects on perception and behavior in both humans and experimental animals. The variability in behavioral responses caused by these fluctuations have real world effects because they can cause an individual to respond inappropriately in high stakes and demanding situations, such as driving a car or operating on a patient. In addition, if not accounted for, the fluctuations can be a source of increased variability in both clinical therapies and systems neuroscience research, reducing the effectiveness of treatments and the robustness of experimental results. So far, much of the progress in understanding the effects of state on neural processing has come from experiments in sensory circuits. But knowing how state affects sensory processing isn’t enough to understand how it affects behavior because there are many additional downstream stages of neural circuit processing before the final motor output. The goal of this project is to examine the effects of state on both sensory and motor systems for the same behavior. This will be accomplished by taking advantage of a sensorimotor task (delay eyeblink conditioning, dEBC) in which much of the processing between sensory and motor systems occurs within a single brain area (the cerebellum). The experiments will involve first developing novel quantitative methods based on psychophysics to test the effects of state on dEBC. Two different types of behavioral state will be examined—locomotion and arousal—and the experiments are designed to tease apart the relative effects of these two states on dEBC. The experiments will then use large scale imaging and electrophysiology to test if and how the input (sensory) and output (motor) neurons of the cerebellum are affected by state. The results of these experiments will provide the first glimpse of how an entire neural system and behavior are dynamically modulated by state on a subsecond to second timescale. A greater understanding of the impact of state on the neural processing underlying behavioral performance will provide critical information for optimizing experimental design and therapies.