Neural circuit mechanisms underlying cognitive control of sensory-guided behavior

感觉引导行为认知控制的神经回路机制

• 批准号: 10592535
• 负责人: David J Margolis
• 金额: $ 37.88万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592535
• 关键词: Address; Anatomy; Area; Behavior; Behavior Control; Behavioral; Behavioral Mechanisms; Brain; Cell Nucleus; Cells; Chronic; Color; Corpus striatum structure; Discrimination; Dorsal; Electrophysiology (science); Fiber; Gilles de la Tourette syndrome; Goals; Huntington Disease; Image; Impairment; Impulsive Behavior; Impulsivity; Interneurons; Knowledge; Learning; Measurement; Measures; Medial; Mediating; Modeling; Motor; Mus; Neural Pathways; Neurons; Obsessive-Compulsive Disorder; Parvalbumins; Pathway interactions; Pattern; Performance; Photometry; Play; Population; Population Dynamics; Role; Sensory; Shapes; Signal Transduction; Site; Slice; Somatosensory Cortex; Synapses; Synaptic plasticity; System; Tactile; Task Performances; Testing; Texture; Thalamic Nuclei; Thalamic structure; Touch sensation; Vibrissae; Work; base; behavior influence; behavioral response; cell type; cognitive control; experimental study; in vivo; in vivo imaging; learned behavior; mouse model; neocortical; nerve supply; nervous system disorder; neural circuit; optogenetics; patch clamp; relating to nervous system; response; two-photon

SUMMARY The ability to make appropriate actions, as well as to inhibit unbeneficial actions, is a key aspect of sensorimotor learning. Our recent work has used the mouse whisker system as model for sensory-guided learning to identify an important and previously unknown role for synaptic input from primary somatosensory cortex (S1) to the dorsal striatum (DStr) as a substrate for response inhibition. This renewal proposal aims to test the idea that the relative synaptic innervation of striatal parvalbumin-expressing (PV) interneurons compared to the spiny projection neurons (SPNs) is a circuit mechanism for behavioral response inhibition. We will use a suite of in vivo imaging and optogenetics experiments, as well as ex vivo electrophysiology experiments to measure and manipulate neural circuitry from two important brain areas: S1 and thalamic posterior medial nucleus (POm) to test their roles in modulation of DStr. Preliminary results suggest that S1 and POm influence behavioral performance of a texture discrimination task in opposing ways, allowing for focused tests of our hypotheses of the synaptic circuitry mediating these learned behaviors. Our integrative in vivo and ex vivo approach, combining manipulation of specific neural pathways, longitudinal tracking of genetically identified neurons, anatomical analysis, and ex vivo synaptic measurements will allow us to investigate the neural circuit basis of learned response inhibition at a scale not before achieved. A major goal is to address the gap in knowledge on the roles of S1 and POm projections to the striatum and their influence on behavior. The results will have implications for the neural circuitry underlying cognitive control, which will aid our understanding the basis of neurological disorders involving deficits in cognitive control.

概括 采取适当的行动以及抑制无负责动作的能力是感觉运动的关键方面 学习。我们最近的工作将鼠标晶须系统作为感觉引导学习的模型 从主要体感皮质（S1）到该突触输入的重要且以前未知的作用 背侧纹状体（DSTR）作为反应抑制的底物。该更新提案旨在测试 与刺相比，纹状体细胞蛋白表达（PV）中间神经元的相对突触神经 投影神经元（SPN）是行为反应抑制的电路机制。我们将使用一套 体内成像和光遗传学实验，以及体内电生理学实验，以测量和 从两个重要的大脑区域操纵神经回路：S1和丘脑后内侧核（POM）到 测试它们在DSTR调制中的作用。初步结果表明S1和POM会影响行为 以相反的方式执行纹理歧视任务 介导这些学习行为的突触电路。我们的体内和离体方法，结合 操纵特定神经途径，遗传鉴定神经元的纵向跟踪，解剖学 分析和离体突触测量将使我们能够研究学习的神经回路基础 在无法实现之前无法进行的响应抑制。一个主要目标是解决有关角色知识的差距 S1和POM对纹状体的预测及其对行为的影响。结果将对 认知控制的神经回路，这将有助于我们理解神经系统的基础 涉及认知控制缺陷的疾病。