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

项目摘要 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，它们在分布式大脑之间的神经信息交流中发挥着核心作用， 在复杂的认知过程中，如注意力。去极化神经振荡活动是 经常报告精神疾病，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。对潜在的电路机制知之甚少 驱动支持注意力的神经振荡，或者它们是如何被破坏以产生去兴奋化的。我们 一个全面的想法，以帮助恢复注意力是采取一种基于电路的方法， 皮质区域恢复到健康状态，随后重新建立适当的注意力表现。这项建议 目的是确定新的电路机制驱动同步神经振荡所需的注意力。我们 初步研究发现，前扣带回皮质自上而下投射的化学发生失活 大脑皮层（ACC）到视觉皮层（维斯）的信号传导干扰小鼠的视觉注意行为。此外，我们表明， 这种自上而下的电路的电路特异性光遗传学激活增强了注意力表现。值得注意的是， 关注 15q13.3 显著 精神分裂症 是 微缺失， 或 缺陷和皮质伽马振荡减少 微缺失是一种主要的拷贝数，有充分的证据表明与一种 少数人被诊断患有各种神经发育障碍，如自闭症， 虽然我们的初步结果暗示了注意力控制的回路特异性机制， 尚不清楚1）注意期间和15 q13.3时ACC维斯活性是否增加 2)ACC-VIS同步化与注意力相关，并被15q13.3微缺失破坏， 如果3）自上而下的回路可以被调节以挽救注意力缺陷。 据报道，在小鼠中， 变体 被破坏 我们假设这个前额叶 自上而下投射到视皮层，在注意过程中激活了ACC和维斯之间的活动， 可以利用ACC脑维斯投射来改善由15 q13.3引起的同步和注意力缺陷 微缺失我们的实验设计使用交叉病毒方法和尖端纤维 光度法、体内电生理学和光遗传学技术，以同时监测和操纵 这种自上而下的电路作为小鼠执行一个自然的自由移动的注意力任务，以测试这一假设。我们 我预计我们的研究将为神经同步的作用提供新的基本机制见解 并提供了一个独特的机会，以确定新的电路为基础的目标，神经调节 精神疾病的治疗。

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.