Distributed Neural Activity Patterns Underlying Practice-Based Learning

基于实践的学习的分布式神经活动模式

• 批准号: 10447345
• 负责人: Kimberly Reinhold
• 金额: $ 11.74万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447345
• 关键词: Animals; Anxiety; Area; Association Learning; BRAIN initiative; Basal Ganglia; Behavior; Behavioral Paradigm; Brain; Calcium; Cells; Color; Cues; Data; Detection; Electrophysiology (science); Environment; Feedback; Food; Forelimb; Goals; Image; Label; Learning; Link; Measures; Memory; Methods; Microscope; Modeling; Motor; Mus; Neurons; Outcome; Output; Pathway interactions; Pattern; Persons; Phase; Population; Post-Traumatic Stress Disorders; Postdoctoral Fellow; Process; Psychological reinforcement; Reporter; Retina; Sensory; Shapes; Short-Term Memory; Smell Perception; Smoking; Synapses; Synaptic plasticity; System; Techniques; Testing; Update; Visual; Visual Cortex; Visual Pathways; Work; addiction; autism spectrum disorder; base; cigarette smoke; cognitive function; cognitive process; experience; experimental study; fluorophore; in vivo; in vivo two-photon imaging; innovation; insight; learned behavior; loss of function; motor behavior; motor control; nicotine reward; optogenetics; recruit; relating to nervous system; response; superior colliculus Corpora quadrigemina; supervised learning; tool; two-photon

PROJECT SUMMARY / ABSTRACT To survive, animals must learn appropriate associations between sensory cues and motor actions through a process of trial and error. We expect that this learning will strengthen the synaptic connections between neurons representing the sensory cue and neurons initiating the motor action. The strengthened synapses may be direct synaptic connections between these neuronal populations or via systems intermediate between these neurons, i.e., a “plastic brain circuit” or “pathway.” Synaptic plasticity has been observed in many different brain areas, and the mechanisms are moderately well understood. However, we have struggled to identify which plastic brain circuit underlies, specifically, the sensory cue-to-motor action association that is learned through the process of trial and error. This is due, in part, to the fact that many brain areas undergo plastic changes during learning, as the experience of learning recruits a variety of different cognitive processes, including sensory detection, motor control, feedback, working memory and reinforcement learning -- cognitive processes that all engage different brain areas and distributed networks. During my postdoc, I developed an approach to assign these cognitive functions to different brain circuits for a case of trial and error learning in mice. The approach involved an innovative behavior paradigm and optogenetic tools that are spatially and temporally precise. Mice learned to associate the optogenetic activation of visual cortex (cue) with a forelimb reach to grab a food pellet (motor action). As a result of my postdoc work, I now know which neurons in the brain encode this cue and which are required to initiate this motor action. Therefore I am now equipped to identify the plastic brain circuit underlying the learned association between this cue and this action. Here I propose to study the brain circuit between the cue-encoding neurons and the neurons necessary to initiate the motor action, in vivo while mice learn the cue-action association. I will study the flow of neural activity from the cue- encoding neurons in the visual cortex to the neurons in the superior colliculus that are necessary to initiate the motor action. In Aim 1, I will identify changes in the cued activity in visual cortex over learning. In Aim 2, I will determine how activity in the superior colliculus changes over learning. In Aim 3, I will determine whether the output of this pathway is sufficient to trigger the motor action after learning. Hence this work speaks directly to a key goal of the Brain Initiative, to “demonstrate causal links between brain activity and behavior.” I will learn in vivo two-photon imaging for Aim 1 under the guidance of Dr. Sabatini, an expert at this technique. Aims 2 and 3 will be conducted in the independent phase using in vivo electrophysiology, a technique with which I have extensive experience. These experiments will help to identify a pathway from visual cortex to superior colliculus that stores a learned, associative memory. Finding the neural basis of learned, sensory cue-motor action associations will be essential to treat specific harmful associations, such as occur in PTSD, OCD, autism and anxiety, without generally disrupting sensory or motor behavior.

项目摘要 /摘要 为了生存，动物必须通过A。感官提示和运动动作之间的适当关联。 反复试验的过程。 神经元抑制感官提示和神经元引发运动动作的神经元。 是这些神经元种群之间的直接突触连接，或通过系统中间的系统 神经元，即“塑料脑电路”或“途径”。 领域，机制众所周知。 塑料脑电路下属，特别是感官提示到运动动作 反复试验的过程。 在学习过程中，随着学习的经验招募了各种不同的认知过程， 感官检测，运动控制，反馈，工作记忆和增强学习 - 认知过程 所有这些都吸引了不同的大脑区域和分布式网络。 将这些认知功能分配给不同的大脑回路，以进行小鼠的反复试验 方法涉及创新的行为范式和光遗传学工具工具工具 精确的小鼠学会了将视觉皮层（CUE）的光遗传学激活与前肢接触。 抓住食物颗粒（运动动作）。 编码此提示，并且需要该提示来启动此电动机动作。 塑料脑电路是提示与该动作之间学到的关联的基础。 研究提示编码神经元之间的大脑回路和启动电动机的必要条件 动作，在体内学习提示性协会时。 在上丘中的神经元中编码视觉皮层中的神经元是启动您所必需的 运动动作。 确定在AIM 3中的上级学习中的活动。 该路径的输出是补充学习后触发电动机动作的补充。 大脑计划的关键目标是“展示大脑活动和行为之间的因果关系” 在thechnique的专家Sabatini博士的指导下，IAM 1的体内两光子成像 3将在独立阶段使用体内电生理学进行，这是I的技术 拥有丰富的经验。 存储有学识渊博的记忆的胶囊。 行动协会对于信任特定的危害协会至关重要，例如在PTSD，OCD，OCD，OCD， 自闭症和焦虑，而不必破坏感觉或运动行为。