Manipulation and imaging of synchronous population activity in the neocortex

描述（由申请人提供）：了解像新皮层这样的大规模互联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。关于新皮层中信息处理的持续争论的核心是关于新皮层网络中使用的神经元代码的性质的问题，即是脉冲速率还是精确定时的同步脉冲模式携带和处理信息。有大量的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编码运动事件，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，同步新皮层活动的神经生理机制尚不清楚。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，我们对同步新皮层活动的产生和传播的大部分知识都是基于理论研究，因为生物网络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的光学方法来研究新皮层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层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，以监测单个神经元的反应以及体外皮层网络中同步和非同步群体活动的传播。人类认知障碍（如精神分裂症或自闭症谱系障碍）的神经生理学基础尚不清楚。一种尚未探索的可能性是，新皮层网络产生、处理和传播同步群体活动的能力——这被认为在高级皮层功能中起着关键作用——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。这可能会对认知障碍的神经病理学产生有价值的新见解，并激发新的治疗策略。

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.