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

• 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
• 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

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.

项目摘要 新皮层的神经活动在一定的时间尺度上是可塑的。学习之间的关联 感觉刺激和行为相关的结果驱动皮层可塑性，是生物体的基础， 生存慢性压力也会影响神经回路，尽管它对感觉皮层连接的贡献 感觉编码也不清楚新皮层中信息处理的变化可以发生在不同的 空间尺度：在由异质性兴奋性和抑制性细胞类型组成的局部微电路中， 相互连接的皮层网络过去十年的啮齿动物研究揭示了一个复杂的网络， 可能涉及视觉引导行为的次要视觉区域，例如 视觉刺激与厌恶事件。然而，这些次级区域的动态网络连通性和 它们对习得的、视觉引导的恐惧行为的独特贡献是未知的。恐惧学习增强了 预测足部电击的刺激的皮质表征，但目前尚不清楚是否不同的抑制性 元素支持视觉刺激表示中的这些变化。 使用创新的成像方法，该提案将解决3个目标：（1）确定 网络动态和功能连接伴随着恐惧学习。拟议的实验将 研究初级和次级视觉皮层对学习恐惧行为的贡献 双光子/宽场成像和皮质失活方法。(2)确定微电路， 与恐惧学习相关的皮层反应变化使用细胞类型特异性双光子成像， Moberly博士将测试VIP介导的去抑制增强皮层输出神经元的假设 应答(3)研究应激对功能性感觉皮层网络结构的影响， 它与正在进行的行为状态的关系。 Moberly博士将在他的导师Jessica Cardin博士和Michael Higley博士的实验室进行这项研究 在耶鲁大学医学院，咨询委员会成员玛丽娜·皮乔托博士（Marina Picciotto） 和迈克尔·克雷在K99期间，Moberly博士将学习细胞双光子的新技术， 联合光遗传学和定量行为学的同时双光子/宽视野成像 接近。拟议的实验和多方面的培训计划将赋予博士。 这些技能的组合将使他能够过渡到一个成功的独立职业生涯， 神经学家