Dynamic regulation of thalamic processing

描述（由申请人提供）：新皮质接收来自两类丘脑核的输入。一级（“特定”）核向新皮层传递来自外周的感觉输入。高阶（“非特异性”）丘脑核接收并向各种皮层区域提供输入。基于令人兴奋的新数据，我们假设这种二分法过于简单，因为高阶核也作为从外周到皮层和皮层下结构的感觉输入的重要中继。我们将表明，高阶核——特别是后内侧核（POm），体感觉系统的高阶核——的感觉处理是由一个关键的丘脑下核——无隔带（ZI）调节的。我们将进一步证明，ZI对POm的抑制调节是由与睡眠-觉醒状态相关的脑干胆碱能输入和与随意运动相关的相运动皮层输入动态调节的。这种状态依赖门控（SDG）假说与理解所有“高阶”丘脑核的功能有关，因为它们都受到ZI的有效抑制。由于ZI和POm都与各种运动障碍有关，预期的发现可能与理解帕金森病等疾病的发病机制有关。

DESCRIPTION (provided by applicant): The neocortex receives inputs from two classes of thalamic nuclei. First-order ("specific") nuclei relay to the neocortex sensory inputs from the periphery. Higher-order ("non-specific") thalamic nuclei receive and provide inputs to various cortical areas. Based on exciting new data we hypothesize that this dichotomy is overly simplistic, in that higher-order nuclei function also as important relays of sensory inputs from the periphery to cortical and subcortical structures. We will show that sensory processing by higher-order nuclei-specifically the posterior medial nucleus (POm), the higher-order nucleus of the somatosensory system-is regulated by a critical subthalamic nucleus - the zona incerta (ZI). We will further show that ZI's inhibitory regulation of POm is dynamically modulated by brainstem cholinergic inputs related to sleep-wake states, and by phasic motor cortex inputs related to voluntary movements. This State Dependent Gating (SDG) hypothesis is relevant to understanding the functions of all "higher-order" thalamic nuclei, as they are all subject to potent inhibition from ZI. Because both ZI and POm are implicated in various movement disorders, the anticipated findings may be relevant for understanding the pathogenesis of disorders such as Parkinson's disease.