Dynamic regulation of thalamic processing

描述(申请人提供)：新皮质接受来自两类丘脑核团的输入。一级(“特定”)核团从外周传递到新皮质的感觉输入。丘脑高级(“非特异性”)核团接受并向不同的皮质区域提供信息。基于令人兴奋的新数据，我们假设这种二分法过于简单化，因为更高阶的核团也是感觉输入从外周到皮质和皮质下结构的重要中继站。我们将展示高阶核团--特别是后内侧核(POM)，即躯体感觉系统的高阶核团--的感觉处理，受到关键的丘脑底核--未确定带(Zi)的调节。我们将进一步证明，ZI对POM的抑制调节是由与睡眠-觉醒状态有关的脑干胆碱能输入和与自愿运动有关的相运动皮质输入动态调节的。这一状态依赖门控(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，预期的发现可能有助于理解帕金森氏病等疾病的发病机制。

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.