Ensemble Recording in Corticostriatal Pathways During Procedural Learning

程序学习期间皮质纹状体通路的整体记录

• 批准号: 7614728
• 负责人: Kyle S Smith
• 金额: $ 4.68万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7614728
• 关键词: Agonist; Allatostatin; Area; Arts; Basal Ganglia; Base of the Brain; Behavior; Behavioral; Brain; Complex; Corpus striatum structure; Development; Disease; Drug Addiction; End Point; Event; Exhibits; Fire - disasters; Functional disorder; Genes; Genetic; Gilles de la Tourette syndrome; Goals; Habits; Huntington Disease; Injection of therapeutic agent; Learning; Lesion; Maintenance; Medial; Methods; Muscimol; Neocortex; Neurons; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Outcome; Parkinson Disease; Pathway interactions; Pattern; Performance; Physiology; Population; Prefrontal Cortex; Procedures; Process; Rate; Rattus; Reporting; Research; Response to stimulus physiology; Rewards; Role; Site; Source; Staging; Structure; Techniques; Testing; Time; Training; Viral Vector; Work; base; behavior test; day; disability; habit learning; motor disorder; neocortical; network models; relating to nervous system; research study; response; skills; tool

DESCRIPTION (provided by applicant): Mounting evidence indicates that procedural learning and habit formation require a restructuring of neural activity patterns in anatomical loops connecting the cortex with the striatum of the basal ganglia. Yet remarkably little is known about where and how these critical activity changes take place. This is a pressing issue for modern research and the broad goal of my proposed work. Technological advancements have now made it possible to record or silence the activity of large populations of neurons in spatially segregated brain areas at the same time. Harnessing these new tools, I will first simultaneously evaluate neural activity in cortex sites (infralimbic and premotor) and striatum sites (dorsolateral striatum) identified in brain lesion studies as critical nodes in the larger brain network for habit formation as rats are extensively trained on a maze task. This will allow me, for the first time, to track the restructuring of neural activity that encodes procedural learning and habits in both cortex and striatum, as well as evaluate the flow of information within corticostriatal loops as learning progresses. I will subsequently incorporate new gene-based methods to silence the activity of one habit site (in the infralimbic cortex), a procedure that is known to block habit-based behaviors, while simultaneously recording from neurons in another (in the dorsolateral striatum). In this way, I can evaluate how neural activity patterns that emerge with habit formation become delayed or obstructed when vital pathways of the cortex- basal ganglia are 'short circuited'. Finally, throughout the proposed I will incorporate anatomical tracing techniques to identify crucial circuit connections for learning-related plasticity within these sites, and will also include tests of behavioral sensitivity to reward value at different learning stages to evaluate the transition of behavior from 'goal-directed' or 'habitual' as formally defined. This research will use state-of-the art genetic and physiology techniques to identify the critical patterns of activity that emerge in the cortex and basal ganglia when a skill is learned and becomes a habit with practice. Understanding the brain basis of normal habit learning will be key to understanding how abnormalites of brain activity contribute to behavioral disabilities (e.g. in Parkinson's and Huntington's Disease) and compulsions (e.g., in drug addiction and obsessive-compulsive spectrum disorders).

描述（由申请人提供）：越来越多的证据表明，程序性学习和习惯形成需要对连接皮层和基底神经节纹状体的解剖环路中的神经活动模式进行重组。然而，人们对这些关键活动变化发生的地点和方式知之甚少。这是现代研究的一个紧迫问题，也是我提出的工作的广泛目标。现在，技术进步使得同时记录或抑制空间隔离的大脑区域中大量神经元的活动成为可能。利用这些新工具，我将首先同时评估皮层部位（边缘下和前运动）和纹状体部位（背外侧纹状体）的神经活动，这些部位在脑损伤研究中被确定为更大的大脑网络中习惯形成的关键节点，因为大鼠受到广泛的训练迷宫任务。这将使我第一次能够跟踪编码皮质和纹状体中的程序性学习和习惯的神经活动的重组，并随着学习的进展评估皮质纹状体环路内的信息流。随后，我将采用新的基于基因的方法来沉默一个习惯位点（在边缘下皮层）的活动，这一过程已知可以阻止基于习惯的行为，同时记录另一个习惯位点（在背外侧纹状体）的神经元。通过这种方式，我可以评估当皮层基底神经节的重要通路“短路”时，随着习惯形成而出现的神经活动模式如何被延迟或阻碍。最后，在整个提议中，我将结合解剖追踪技术来识别这些位点内与学习相关的可塑性的关键回路连接，并且还将包括不同学习阶段对奖励价值的行为敏感性测试，以评估从“目标-”的行为转变。正式定义的“定向”或“习惯”。这项研究将使用最先进的遗传和生理学技术来识别当学习技能并通过练习成为习惯时皮质和基底神经节中出现的关键活动模式。了解正常习惯学习的大脑基础将是了解大脑活动异常如何导致行为障碍（例如帕金森病和亨廷顿病）和强迫行为（例如吸毒成瘾和强迫谱系障碍）的关键。