Dynamic regulation of thalamic processing

描述（由申请人提供）：新皮层接收来自两类丘脑核团的输入。一级（“特定”）核团将来自外围的感觉输入中继到新皮层。高级（“非特异性”）丘脑核接收并向各个皮质区域提供输入。基于令人兴奋的新数据，我们假设，这种二分法是过于简单化，在高阶核团的功能也作为重要的继电器的感觉输入从外围到皮层和皮层下结构。我们将表明，高级核团的感觉处理，特别是后内侧核（POm），高级核团的躯体感觉系统，是由一个关键的丘脑底核-（ZI）。我们将进一步表明，ZI的抑制性调节POm动态调制脑干胆碱能输入相关的睡眠-觉醒状态，并通过相位运动皮层输入相关的自愿运动。这种状态依赖性门控（SDG）假说与理解所有“高级”丘脑核团的功能有关，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，因此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.