Coding and processing of error signals in inferior olivary-cerebellar networks

下橄榄小脑网络中误差信号的编码和处理

• 批准号: 10522031
• 负责人: JAVIER F MEDINA
• 金额: $ 57.42万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-02 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522031
• 关键词: Affective; Afferent Pathways; Animals; Anterior; Area; Ataxia; Attention; Attention deficit hyperactivity disorder; Behavior; Blinking; Brain; Brain region; Cell Nucleus; Cells; Cerebellar Cortex; Cerebellar Diseases; Cerebellum; Cerebral cortex; Code; Cognition Disorders; Cognitive; Communication; Communication impairment; Conditioned Stimulus; Cues; Disease; Dorsal; Dystonia; Educational process of instructing; Event; Fiber; Future; Goals; Heterogeneity; Individual; Inferior; Instruction; Learning; Link; Machine Learning; Mental Processes; Molecular Target; Motor; Movement; Mus; Neurologic; Neuronal Plasticity; Neurons; Occupations; Olives - dietary; Pathway interactions; Play; Pontine structure; Prefrontal Cortex; Process; Protocols documentation; Purkinje Cells; Research; Rest; Role; Schizophrenia; Sensory; Short-Term Memory; Signal Transduction; Somatosensory Cortex; Source; Specificity; Stimulus; Syndrome; Testing; Time; Training; Update; Work; autism spectrum disorder; base; cognitive function; density; expectation; experimental study; eyeblink conditioning; insight; mossy fiber; motor control; motor learning; nervous system disorder; neuromechanism; neuropsychiatric disorder; novel therapeutic intervention; optogenetics; relating to nervous system; response; supervised learning; theories; tool

PROJECT SUMMARY The cerebellum plays a key role in motor control, particularly in motor learning. However, there is increasing recognition that the cerebellum also participates in cognitive functions such as planning, set-shifting, abstract reasoning, attention and working memory. Indeed, cerebellar damage is associated with both motor and cognitive problems and has been linked to a wide range of neurological and neuropsychiatric disorders, from ataxia and dystonia to schizophrenia and autism. Despite this remarkable functional heterogeneity, the cerebellar microcircuit is remarkably homogeneous, both across its different regions and across different animal species. This has led to the theory that the cerebellum may accomplish its job by performing one universal computation, which can be applied to both motor and non-motor functional domains by connecting the cerebellum to different brain areas. Much of what we know about this universal computation comes from mechanistic studies that have revealed what the cerebellum does – and how it does it – by manipulating and recording neural activity in the cerebellum of mice and other animals performing simple sensorimotor learning tasks. Based on this previous work, a picture is emerging that the cerebellum is a ‘machine’ specialized for supervised learning, whose function can be summarized succinctly: to learn how to eliminate errors. While there is good support for this idea for learning tasks in which the error signals are low-level and conveyed directly from the sensory periphery to the cerebellum via subcortical pathways, there is almost nothing known about the function of high-level error signals originating in parts of the brain that are not directly connected to the sensory or motor periphery. The goal of this project is to start filling this gap by examining how the cerebellum operates when mice are trained in 3 new learning tasks recently developed, in which the error signals originate in the primary somatosensory cortex (aim 1), the cerebellum itself (aim 2) and the prefrontal cortex (aim 3). To assess function, the proposed experiments will record and manipulate the error signals present during the learning process with an unprecedented level of temporal and cellular specificity, using new high-density Neuropixels tools and cell-specific photostimulation with optogenetics. This research could help develop new therapeutic approaches to treat both motor as well as cognitive disorders associated with deficient connectivity between the cerebellum and the rest of the brain, not by targeting molecular mechanisms of neural plasticity, but the instructive error-related signals that drive them.

项目总结 小脑在运动控制中起着关键作用，特别是在运动学习中。然而，有越来越多的人 认识到小脑也参与认知功能，如计划、集合转移、抽象 推理、注意力和工作记忆。事实上，小脑损伤既与运动有关，也与 认知问题，并与广泛的神经和神经精神障碍有关，从 从共济失调和肌张力障碍到精神分裂症和自闭症。尽管存在这种显著的功能异构性，但 小脑微电路在不同的区域和不同的区域具有显著的同质性 动物物种。这导致了一种理论，即小脑可以通过执行一项任务来完成其工作 通用计算，既可以应用于运动功能领域，也可以应用于非运动功能领域 小脑到不同的大脑区域。我们对这种通用计算的许多了解都来自于 机械学研究揭示了小脑是做什么的--以及它是如何做的--通过操纵和 记录进行简单感觉运动学习的小鼠和其他动物的小脑神经活动 任务。基于这项先前的工作，出现了一幅图，小脑是一台专门用于 监督学习，其功能可以简单地概括为：学习如何消除错误。而当 对于其中错误信号是低电平并被传递的学习任务，这种想法得到了很好的支持 通过皮质下通路直接从感觉外周到小脑，几乎什么都不知道。 关于起源于大脑不直接连接的部分的高水平错误信号的功能 感觉或运动的外周。这个项目的目标是通过研究 当小鼠在最近开发的3个新的学习任务中进行训练时，小脑运作，其中错误 信号来自初级躯体感觉皮质(目标1)、小脑本身(目标2)和前额叶 皮质(目标3)。为了评估功能，拟议的实验将记录和处理误差信号 在学习过程中以前所未有的时间和细胞特异性呈现，使用新的 高密度神经像素工具和具有光遗传学的细胞特异性光刺激。这项研究可能会有所帮助 开发新的治疗方法来治疗运动和认知障碍，这些障碍与 小脑和大脑其他部分之间的连接不足，而不是通过靶向分子机制 神经可塑性，而是驱动它们的指导性错误相关信号。