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

大脑被认为包含许多预测系统，从简单的感觉-运动相互作用到有意识的规划，跨越了巨大的功能范围。描述预测系统是一项挑战，因为它们与高度可塑性的大脑结构有关，这些结构是共同进化的，而且往往高度相互联系(例如，新皮质与小脑)。然而，这一挑战是值得解决的，因为一个预测系统的功能障碍原则上可以通过推进另一个功能重叠的预测系统来缓解。感觉门控(SG)的经典描述是，身体运动的规划和执行导致外周感觉信号流的调节。该描述已经承担了从中央处理站发送到外围处理站的反馈信号的角色，并且它指出了SG作为预测系统的可能角色。本提案的目标有三个方面。我们首先想要证明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，我们计划阐明它的神经机制，涉及一个皮质球环路，通过它周围的感觉信号受到自上而下的控制。在初步的工作中，我们已经证明了SG不同于状态估计(SE，再传入原理的经典概念)，这两个系统到目前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，我们将在非运动行为元素中对其进行研究，该元素被引入到头部固定的小鼠的爪子伸展-伸出-返回范式中，以及在没有任何动作的奖励期望任务中。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。如果这两个目标都得到支持，将把SG与SE区分开来，并指出SG可能具有的新功能。关于神经元的底物，我们将研究皮质球从新皮质到楔状核的投射，使用皮质投射起源的投射特异性光遗传刺激，以及干扰局部的楔状抑制中间神经元。为了确认我们在有和没有运动系统贡献的情况下处理类似的神经机制，我们将测试它们是否都同样涉及皮质球环和内在楔状神经元的功能。

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.