Cortico-cortical Projections Driving Frontal-sensory Neural Oscillatory Synchrony to Mediate Attention

皮质-皮质投射驱动额感觉神经振荡同步以调节注意力

基本信息

批准号：
10200640
负责人：
Kevin Jay Norman
金额：
$ 1.24万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-02 至 2021-08-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200640
关键词：
Anterior Attention Attentional deficit Automobile Driving Behavior Brain Cognition Complex Copy Number Polymorphism Critical Thinking Data Diagnosis Electrophysiology (science)Exhibits Experimental Designs Fiber Foundations Frequencies Functional disorder Genetic Risk Goals Impaired cognition Individual Intervention Measures Mediating Mental Depression Mental disorders Minority Monitor Mus Neurodevelopmental Disorder Neurons Performance Periodicity Photometry Physiological Play Prefrontal Cortex Psychiatric therapeutic procedure Reaction Time Recovery Reporting Research Role Schizophrenia Scientist Sensory Techniques Testing Therapeutic Time Variant Viral Visual Cortex Visual attention Wild Type Mouse attentional control autism spectrum disorder base cingulate cortex cognitive function cognitive process improved in vivo insight microdeletion neuroregulation novel optogenetics relating to nervous system sensory cortex sensory integration skills sustained attention visual information

项目摘要

Project Summary Neural oscillations had previously been considered to be a consequence of cognitive function, but recent evidence suggests they rather play a central role in communicating neural information across distributed brain networks during complex cognitive processes such as attention. Desynchronized neural oscillatory activity is frequently reported in psychiatric disorders, including autism, depression, and schizophrenia, leading to cognitive impairments, including attentional deficits. Little is known about the underlying circuit mechanisms that drive neural oscillations supporting attention or how they are disrupted to produce desynchronization. Our comprehensive idea to aid in the recovery of attention is to take a circuit-based approach to resynchronize cortical regions to healthy states and subsequently reestablish proper attentional performance. This proposal aims to identify novel circuit mechanisms driving synchronous neural oscillations required for attention. Our preliminary study found that chemogenetic inactivation of top-down cortical projections from anterior cingulate cortex (ACC) to the visual cortex (VIS) disrupts visual attentional behavior in mice. Furthermore, we show that circuit-specific optogenetic activation of this top-down circuit enhances attention performance. Of note, both attention 15q13.3 significant schizophrenia. is microdeletion, or deficits and reduced cortical gamma oscillation microdeletion, one of the major copy number well documented in association with a minority of individuals diagnosed with various neurodevelopmental disorder such as autism and Although our preliminary results implicate a circuit-specific mechanism of attentional control, it unknown whether 1) ACC  VIS activity increased during attention and by 15q13.3 2) ACC-VIS sychronization is associated with attention and disrupted by 15q13.3 microdeletion, if 3) the top-down circuit can be modulated to rescue attention deficits. in mice were reported to be caused by chromosomal variants is disrupted We hypothesize that this prefrontal top-down projection to visual cortex synchronizes activity between ACC and VIS during attention and that ACCVIS projection can be leveraged to improve synchronization and attention deficits caused by a 15q13.3 microdeletion. Our experimental design uses an intersectional viral approach and cutting-edge fiber photometry, in vivo electrophysiology and optogenetic techniques to simultaneously monitor and manipulate this top-down circuit as mice perform a naturalistic free moving attention task to test this hypothesis. We anticipate our study will shed novel fundamental mechanistic insight into the role of neural synchronization during attention and provide a unique opportunity to identify novel circuit-based targets for neuromodulation treatments of psychiatric disorders.

项目概要神经振荡以前被认为是认知功能的结果，但最近有证据表明它们在跨分布式大脑交流神经信息方面发挥着核心作用复杂的认知过程（例如注意力）中的网络是不同步的神经振荡活动。经常报道精神疾病，包括自闭症、抑郁症和精神分裂症，导致认知障碍，包括注意力缺陷，人们对潜在的回路机制知之甚少。驱动支持注意力的神经振荡或它们如何被破坏以产生不同步。帮助恢复注意力的综合想法是采用基于电路的方法来重新同步皮质区域恢复健康状态，随后重新建立适当的注意力表现。旨在识别驱动注意力所需的同步神经振荡的新颖电路机制。初步研究发现，前扣带回自上而下的皮质投射的化学遗传学失活皮层（ACC）到视觉皮层（VIS）会扰乱小鼠的视觉注意力行为。值得注意的是，这种自上而下电路的电路特异性光遗传学激活增强了注意力表现。注意力 15q13.3 重要的精神分裂症。是微缺失, 或者缺陷和皮质伽马振荡减少微缺失，有据可查的与相关的主要拷贝数之一少数被诊断患有各种神经发育障碍的人，例如自闭症和尽管我们的初步结果暗示了注意力控制的特定回路机制，但它未知 1) ACC  VIS 活动在注意力期间和 15q13.3 是否增加 2) ACC-VIS 同步与注意力相关，并被 15q13.3 微缺失破坏，如果3）可以调节自上而下的电路来挽救注意力缺陷。据报道，小鼠中的这种情况是由染色体引起的变体被扰乱了我们发现这个前额叶自上而下投射到视觉皮层使注意力期间 ACC 和 VIS 之间的活动同步，并且 ACCVIS 投影可用于改善 15q13.3 引起的同步和注意力缺陷我们的实验设计采用交叉病毒方法和尖端纤维。光度测定、体内电生理学和光遗传学技术可同时监测和操作当移动的老鼠执行自然主义的自由注意任务时，我们会采用这种自上而下的电路来检验这一假设。预计我们的研究将为神经同步的作用提供新颖的基本机制见解注意力期间并提供独特的机会来识别新的基于电路的神经调节目标精神疾病的治疗。