Circuit mechanisms underlying cortical communications

皮层通信的电路机制

• 批准号: 10001944
• 负责人: Soohyun Lee
• 金额: $ 139.34万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10001944
• 关键词: Animal Behavior; Animals; Area; Behavior; Behavioral; Biological Models; Brain; Cells; Communication; Communication impairment; Cues; Development; Electrophysiology (science); Environment; Feedback; Genetic Techniques; Goals; Heterogeneity; Image; Interneurons; Lead; Mental disorders; Methods; Molecular Genetics; Mutate; Neurons; Pharmacogenetics; Rodent; Sensory; Somatosensory Cortex; Specificity; System; Transgenic Mice; Vibrissae; Viral; experience; high risk; hippocampal pyramidal neuron; inhibitory neuron; insight; interdisciplinary approach; neural circuit; neuropsychiatric disorder; optogenetics; organizational structure; presynaptic; recruit; risk variant; sensorimotor system; sensory cortex; sensory stimulus

Summary In order to understand the principles of long-range connectivity in cortical communication, our efforts have focused on the following two projects. Project 1: Functional connectivity of diverse long-range inputs to the primary somatosensory cortex. To achieve a mechanistic understanding of the functional connectivity of top-down projections to the primary sensory cortex, we have systematically investigated the functional connectivity from the major higher-order cortical areas to the different neuronal types in the primary somatosensory cortex. We found that different higher-order cortical inputs differentially recruit specific subtypes of GABAergic interneurons. Furthermore, this projection specificity to distinct GABAergic neuron subtypes allows the primary somatosensory cortex to parse information from diverse cortical feedback projections. On the basis of this framework, we are investigating how cortical feedback projections to the primary somatosensory cortex are altered in a transgenic mouse line in which one of the neurodevelopmental high-risk genes is mutated. Considering that most neuropsychiatric disorders arise during development, our efforts are focused on the developmental mechanisms of the circuit specificity between cortical areas and within a sensory cortex. Project 2: The structural organization of cortical subnetworks. In the project 2, we aimed to understand the principles that govern the functional heterogeneity of pyramidal neurons in sensory cortex. Neuronal activity in the superficial layer of the primary sensory cortex is highly heterogenous in relation to various aspects of animals behavior. We asked whether functionally heterogeneous subnetworks are constrained by specific long-range and local presynaptic ensembles. This study will provide fundamental insights into the structural organization of the cortical subnetwork of pyramidal neurons that may subserve diverse cortical functions.

总结 为了理解皮层通信中的远程连接的原理，我们的努力集中在以下两个项目上。 项目1：不同长距离输入到初级躯体感觉皮层的功能连接。为了从机制上理解初级感觉皮层自上而下投射的功能连接，我们系统地研究了初级躯体感觉皮层中主要高阶皮层区域与不同神经元类型的功能连接。 我们发现，不同的高阶皮层输入差异招募特定亚型的GABA能中间神经元。此外，这种对不同GABA能神经元亚型的投射特异性允许初级躯体感觉皮质解析来自不同皮质反馈投射的信息。在这个框架的基础上，我们正在研究如何在一个神经发育高危基因突变的转基因小鼠系中改变皮层反馈投射到初级躯体感觉皮层。考虑到大多数神经精神疾病出现在发展过程中，我们的努力集中在皮层区域和感觉皮层内的电路特异性的发展机制。 项目2：皮质子网络的结构组织。 在项目2中，我们旨在了解控制感觉皮层锥体神经元功能异质性的原理。初级感觉皮层浅层的神经元活动与动物行为的各个方面有关，具有高度的异质性。我们问是否功能异质的子网络的限制特定的长程和局部突触前合奏。这项研究将提供基本的见解，锥体神经元的皮质子网络的结构组织，可能有助于不同的皮质功能。