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 新皮层中的神经活性在一系列临时尺度上是塑料。之间的学习协会 感官刺激和行为相关的结果驱动皮质可塑性，对生物的基础是基础 生存。慢性压力也会影响中性电路，尽管其对感觉皮层连接的贡献 感官编码尚不清楚。新皮层中信息处理的变化可以在不同的 空间尺度：在局部微电路中，由异质兴奋性和抑制性细胞类型组成，在较大 互连皮质网络。过去十年来的啮齿动物研究揭示了一个精致的网络 可能参与视觉引导行为的次要视觉区域，例如最初中性 视觉刺激带有厌恶事件。但是，这些次要领域的动态网络连接以及 他们对学习，视觉指导性恐惧行为的独特贡献是未知的。恐惧学习可以增强 预测脚部冲击的刺激的皮质表示，但目前尚不清楚是否有不同的抑制作用 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，该建议将解决3个目标：（1）确定变化 恐惧学习的网络动态和功能连接性。提出的实验将 使用Simpletaneous Dual调查对学习的恐惧行为的主要和次级视觉皮质贡献 2-photon/广场成像和皮质灭活方法。 （2）确定贡献的微电路 与恐惧学习相关的皮质反应变化。使用细胞型特异性2光子成像和 Moberly博士将测试VIP介导的抑制作用增强皮质输出神经元的假设 回答。 （3）研究压力对功能感官皮质网络架构的后果和 它与正在进行的行为状态的关系。 莫伯利博士将在他的导师博士的实验室中进行这项研究。杰西卡·卡丁（Jessica Cardin）和迈克尔·希格利（Michael Higley） 在耶鲁大学医学院，咨询委员会成员Drs的投入。码头皮科托 和迈克尔·克莱尔（Michael Crair）。在K99时期，Moberly博士将学习Cellular 2-Photon和 同时进行双重2光子/广场成像与光遗传学和定量行为结合 方法。拟议的实验和多方面的培训计划将以独特的方式授予Moberly博士 技能的结合，可以使他过渡到成功的独立职业 神经科学家。