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

感觉门控的本质 â 探测离皮质环的功能。

• 批准号: 520098446
• 负责人: Professor Dr. Cornelius Schwarz
• 金额: --
• 依托单位: Werner Reichardt-Centrum für integrative Neurowissenschaften (CIN)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/520098446?language=en
• 关键词: nature; sensory; gating; probing; function

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.

大脑被认为包含许多预测系统，涵盖从简单的感觉运动相互作用到有意识规划的巨大功能范围。描述预测系统是一个挑战，因为它们与高度可塑的大脑结构相关，这些大脑结构共同进化并且往往高度相互关联（例如新皮层与小脑）。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。这个描述已经假定了从中央处理站发送到外围处理站的反馈信号的作用，并且它指出SG作为预测系统的可能作用。本提案的目标有三个方面。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，涉及皮质延髓环路，与外周感觉信号带来的自上而下的控制。在初步的工作中，我们已经表明，SG是不同的状态估计（SE，refference原则的经典概念），两个系统，到目前为止一直在研究的背景下，身体运动。为了开始测试SG的新功能，我们将在引入头部固定小鼠的爪子伸出-返回范例的非运动行为元素中以及在没有任何运动的奖励期望任务中研究它。我们进一步的目的是证明SG的独立性小脑使用光遗传学干扰。这两个目标，如果得到支持，将界定秘书长从SE和指向可能的新功能，秘书长。关于神经元基底，我们将使用皮质投射起源的投射特异性光遗传学刺激以及干扰局部楔状核抑制性中间神经元来研究从新皮质到楔状核的皮质延髓投射。为了证实我们在有和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同样涉及皮质延髓环路和内皮层神经元的功能。