The nature of sensory gating – probing the function of a corticofugal loop.

人们认为大脑包含许多预测系统，其功能范围从简单的感觉运动互动到有意识的计划。描述预测系统是一个挑战，因为它们与高度可塑性的大脑结构相关，这些结构共同进化并倾向于高度互联（例如，新皮层与小脑）。然而，这个挑战是值得解决的，因为一个预测系统的功能失调，原则上可以通过促进另一个具有重叠功能的系统来缓解。感觉门控（SG）的经典描述是身体运动的计划和执行导致外周感觉信号流的调制。这一描述已经假设了从中央到外围处理站发送的反馈信号的作用，并且它指出了SG作为预测系统的可能作用。本建议的目标有三个方面。我们首先要证明SG与其他预测系统的分离。其次，我们试图解释其难以捉摸的行为功能。第三，我们计划阐明其神经元机制，涉及皮质球环，与外围感觉信号带来自上而下的控制。在前期工作中，我们已经证明了SG不同于状态估计（SE，经典的参照原理概念），这两个系统迄今为止一直是在身体运动的背景下研究的。为了开始测试SG的新功能，我们将研究它在非运动行为元素中引入的爪子伸出-返回范式，在头部固定的小鼠中，以及在没有任何运动的奖励期望任务中。我们进一步的目的是利用光遗传干扰来证明SG对小脑的独立性。这两个目标，如果得到支持，将从SE描绘出SG，并指出SG可能的新功能。关于神经元基质，我们将研究皮质球从新皮层到楔形核的投射，使用投射特异性光遗传刺激皮质投射起源，以及干扰局部楔形抑制中间神经元。为了确认我们在有或没有运动系统的情况下处理类似的神经元机制，我们将测试它们是否都相同地涉及皮质球环和内在楔形神经元的功能。

The brain is assumed to contain many predictive systems spanning the enormous functional range from simple sensorimotor interactions to conscious planning. It is a challenge to delineate predictive systems, as they are related to highly plastic brain structures that co-evolved and tend to be highly interconnected (e.g. neocortex vs. cerebellum). The challenge, however, is worth to be tackled, as dysfunction of one predictive system, could in principle alleviated by furthering another one with overlapping function. The classical description of sensory gating (SG) has been that planning and execution of body movement leads to modulation of peripheral sensory signal flow. This description already assumes a role for feedback signals sent from central to peripheral processing stations, and it points to a possible role of SG as a predictive system. The goal of the present proposal is three-pronged. We firstly want to demonstrate the separation of SG from other predictive systems. Second, we attempt to explain its elusive behavioral function. Third we plan to elucidate its neuronal mechanisms, involving a corticobulbar loop, with which peripheral sensory signals are brought under top-down control. In preliminary work we have shown that SG is different from state estimation (SE, the classical concept of reafference principle), two systems that so far always have been studied in the context of body movement. To begin to test novel functions of SG we will study it in non-movement behavioral elements introduced to a paw reach-out-return paradigm in head-fixed mice, as well as with a reward expectation task devoid of any movement. We further aim to demonstrate SG’s independence from cerebellum using optogenetic interference. Both aims, if supported, will delineate SG from SE and point to possible novel functions to SG. With respect to the neuronal substrate we will study the corticobulbar projection from neocortex to the cuneate nucleus using projection-specific optogenetic stimulation of cortical projection origins, as well as interfering with local cuneate inhibitory interneurons. To affirm that we deal with comparable neuronal mechanisms in situations with and without contribution of the motor system, we will test whether they all identically involve functions of corticobulbar loop and intrinsic cuneate neurons.