Fear learning-related reconfiguration of local and large-scale cortical networks

局部和大规模皮层网络的恐惧学习相关重构

基本信息

批准号：
10722925
负责人：
Andrew Moberly
金额：
$ 10.2万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722925
关键词：
Advisory Committees Amygdaloid structure Area Arousal Association Learning Basic Science Behavior Behavioral Brain Brain region Chronic stress Committee Members Cues Disinhibition Elements Event Fright Functional disorder Glucocorticoids Goals Image Interneurons Lateral Learning Limbic System Link Mediating Memory Mentors Modality Modeling Molecular Mus Neocortex Neurons Organism Outcome Output Phase Play Population Heterogeneity Population Projection Positioning Attribute Property Punishment Research Rewards Rodent Role Route Sensory Shapes Shock Signal Transduction Stimulus Stress Structure Synapses System Technical Expertise Testing Training Universities Visual Visual Cortex Visual System Visual evoked cortical potential Work area striata career cell type experimental study extrastriate visual cortex flexibility foot imaging approach information processing innovation insight learned behavior maladaptive behavior medical schools multiphoton imaging neocortical network architecture neural neural circuit neuroregulation novel optogenetics response sensory cortex sensory stimulus skills stressor two-photon visual information visual processing visual stimulus

项目摘要

PROJECT SUMMARY Neural activity in the neocortex is plastic over a range of temporal scales. Learning associations between sensory stimuli and behaviorally relevant outcomes drives cortical plasticity and is fundamental to an organism’s survival. Chronic stress can also impact neural circuits although its contributions to sensory cortex connectivity and sensory encoding is unclear. Changes in information processing in the neocortex can take place at different spatial scales: in local microcircuits made up of heterogeneous excitatory and inhibitory cell types and in larger interconnected cortical networks. Rodent studies from the last decade have revealed an elaborate network of secondary visual areas that may be involved in visually-guided behaviors such as associating initially neutral visual stimuli with aversive events. However, the dynamic network connectivity of these secondary areas and their distinct contributions to learned, visually guided fear behavior is unknown. Fear-learning enhances the cortical representation of stimuli that predict a foot shock, but it is currently unknown if different inhibitory elements support these changes in visual stimulus representations. Using innovative imaging approaches this proposal will address 3 Aims: (1) Determine the changes in network dynamics and functional connectivity that accompany fear learning. The proposed experiments will investigate primary and secondary visual cortical contributions to learned fear behavior using simultaneous dual 2-photon/widefield imaging and cortical inactivation approaches. (2) Determine the microcircuits that contribute to fear-learning related changes in cortical responses. Using cell-type specific 2-photon imaging and optogenetics Dr. Moberly will test the hypothesis that VIP-mediated disinhibition enhances cortical output neuron responses. (3) Investigate the consequences of stress for functional sensory cortical network architecture and its relationship to ongoing behavioral state. Dr. Moberly will conduct this research in the labs of his mentors Drs. Jessica Cardin and Michael Higley at the Yale University School of Medicine with input from advisory committee members, Drs. Marina Picciotto and Michael Crair. In the K99 period, Dr. Moberly will learn new technical skills in cellular 2-photon and simultaneous dual 2-photon/widefield imaging in combination with optogenetics and quantitative behavioral approaches. The proposed experiments and multifaceted training plan will impart Dr. Moberly with a unique combination of skills that will position him to transition into a successful independent career as a systems neuroscientist.

项目概要新皮质中的神经活动在一系列时间尺度上是可塑的。感觉刺激和行为相关的结果驱动皮质可塑性，并且是有机体的基础慢性压力也会影响神经回路，尽管它有助于感觉皮层的连接。新皮质信息处理的变化可能发生在不同的地方，目前尚不清楚。空间尺度：由异质兴奋性和抑制性细胞类型组成的局部微电路以及更大的过去十年的啮齿动物研究揭示了一个复杂的皮质网络。次要视觉区域最初可能涉及视觉引导行为，例如联想中性然而，这些次要区域和视觉刺激的动态网络连接。它们对习得的、视觉引导的恐惧行为的独特贡献尚不清楚。预测足部电击的刺激的皮质表征，但目前尚不清楚不同的抑制是否元素支持视觉刺激表征的这些变化。使用创新的成像方法，该提案将实现 3 个目标：(1) 确定伴随恐惧学习的网络动力学和功能连接。使用同步双重研究主要和次要视觉皮层对习得恐惧行为的贡献 2 光子/宽场成像和皮质失活方法 (2) 确定有助于的微电路。使用细胞类型特异性 2 光子成像和恐惧学习相关的皮质反应变化。光遗传学 Moberly 博士将测试 VIP 介导的去抑制增强皮质输出神经元的假设 (3) 研究压力对功能性感觉皮层网络结构的影响和它与持续行为状态的关系。莫伯利博士将在他的导师杰西卡·卡丁博士和迈克尔·希格利博士的实验室中进行这项研究。在耶鲁大学医学院咨询委员会成员 Marina Picciotto 博士的意见下在 K99 期间，Moberly 博士将学习细胞 2 光子和 Michael Crair 方面的新技术技能。结合光遗传学和定量行为学的同步双 2 光子/宽场成像所提出的实验和多方面的培训计划将赋予莫伯利博士独特的能力。多种技能的组合将使他能够作为系统人员过渡到成功的独立职业生涯神经科学家。