Manipulation and imaging of synchronous population activity in the neocortex

新皮质同步群体活动的操纵和成像

• 批准号: 8228410
• 负责人: DETLEF H HECK
• 金额: $ 22.22万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8228410
• 关键词: Address; Attention; Auditory; Behavior; Biological; Brain; Brain Part; Cells; Cerebral cortex; Code; Cognition Disorders; Cognitive; Communication; Complex; Computer software; Data; Data Analyses; Disease; Dyes; Event; Generations; Human; Image; In Vitro; Individual; Knowledge; Lead; Light; Monitor; Motor; Mus; Nature; Neocortex; Neurons; Neurosciences; Optics; Pattern; Play; Population; Process; Schizophrenia; Sensory; Site; Source; Synapses; System; Technology; Testing; Theoretical Studies; Time; Travel; Vibrissae; Visual; Xenon; autism spectrum disorder; barrel cortex; base; charge coupled device camera; cognitive function; data acquisition; digital; improved; information processing; insight; millisecond; mouse model; neocortical; neuropathology; neurophysiology; neuropsychiatry; response; spatiotemporal; tool; treatment strategy; voltage

DESCRIPTION (provided by applicant): Understanding neuronal information processing and neuronal communication in massively interconnected networks like the neocortex is one of the great challenges of neuroscience. At the center of an ongoing debate about information processing in the neocortex is the question about the nature of the neuronal code used in the neocortical network, i.e. whether spike rates or precisely timed synchronous spike patterns carry and process information. There is substantial experimental evidence supporting the functional significance of synchronous spiking activity. Synchronized spikes have been shown to encode motor events, to represent visual, auditory and gustatory sensory information and to correlate with cognitive functions such as attention. However, the neurophysiological mechanisms underlying synchronized neocortical activity are only poorly understood. Two important open questions are: How sensitive are cortical neurons to synchronous synaptic inputs? When and how does synchronous activity propagate through the cortical network? Currently, most of our knowledge about the generation and propagation of synchronous neocortical activity is based on theoretical studies, as experimental approaches in biological networks have been technically challenging. Here we propose a powerful new optical approach to investigate the neurophysiological bases of synchronized activity in the neocortex. The approach uses our newly developed digital light processing (DLP)-based dynamic photo- stimulation system that allows the spatiotemporal control of in vitro cortical network activity using 786,000 independently controlled photo-stimulation sites. Dynamic photo-stimulation will be combined with voltage sensitive dye (VSD) imaging and intracellular electrophysiological recordings to monitor individual neuronal responses and the propagation of synchronized and un-synchronized population activity in the in vitro cortical network. The neurophysiological bases of human cognitive disorders such as schizophrenia or autism spectrum disorders are only poorly understood. A yet unexplored possibility is that the neocortical network's ability to generate, process and propagate synchronous population activity - which is believed to play a key role in higher cortical functions - is altered. Our approach provides new opportunities to investigate potential pathological changes in the processing of synchronous neuronal events in mouse models of human cognitive disorders. This might lead to valuable new insights into the neuropathology of cognitive disorders and inspire new treatment strategies. PUBLIC HEALTH RELEVANCE: The cerebral cortex is the part of the brain most implicated in cognitive brain function and in a diseased state with neuropsychiatric disorders. How information is processed in this complex network of billions of neurons is yet poorly understood, partly due to a lack of appropriate experimental tools to investigate the complex orchestration of activities in individual neurons, which generate the network activity that produces normal behavior. This proposal is to develop and improve an experimental tool that will allow us to address these essential questions using digital light processing technology to mimic network activity patterns of arbitrary complexity and their effects on individual cells and network activity.

描述（由申请人提供）：了解像新皮质这样的大规模互连网络中的神经元信息处理和神经元通信是神经科学的巨大挑战之一。关于新皮质信息处理的持续争论的核心是新皮质网络中使用的神经元代码的性质问题，即尖峰速率或精确定时的同步尖峰模式是否携带和处理信息。有大量实验证据支持同步尖峰活动的功能意义。同步尖峰已被证明可以对运动事件进行编码，代表视觉、听觉和味觉感官信息，并与注意力等认知功能相关。然而，人们对同步新皮质活动背后的神经生理学机制知之甚少。两个重要的悬而未决的问题是：皮质神经元对同步突触输入有多敏感？同步活动何时以及如何通过皮质网络传播？目前，我们关于同步新皮质活动的产生和传播的大部分知识都基于理论研究，因为生物网络中的实验方法在技术上具有挑战性。在这里，我们提出了一种强大的新光学方法来研究新皮质同步活动的神经生理学基础。该方法使用我们新开发的基于数字光处理 (DLP) 的动态光刺激系统，该系统允许使用 786,000 个独立控制的光刺激位点对体外皮质网络活动进行时空控制。动态光刺激将与电压敏感染料（VSD）成像和细胞内电生理记录相结合，以监测个体神经元反应以及体外皮质网络中同步和不同步群体活动的传播。人们对精神分裂症或自闭症谱系障碍等人类认知障碍的神经生理学基础知之甚少。一种尚未探索的可能性是，新皮质网络生成、处理和传播同步群体活动的能力——被认为在高级皮质功能中发挥着关键作用——被改变了。我们的方法为研究人类认知障碍小鼠模型中同步神经元事件处理的潜在病理变化提供了新的机会。这可能会给认知障碍的神经病理学带来有价值的新见解，并激发新的治疗策略。 公共卫生相关性：大脑皮层是大脑中与认知脑功能最相关的部分，并且处于神经精神疾病的患病状态。人们对这个由数十亿个神经元组成的复杂网络中如何处理信息知之甚少，部分原因是缺乏适当的实验工具来研究单个神经元活动的复杂编排，这些活动产生了产生正常行为的网络活动。该提案旨在开发和改进一种实验工具，使我们能够使用数字光处理技术来模拟任意复杂性的网络活动模式及其对单个细胞和网络活动的影响来解决这些基本问题。