WATCHING ACTION POTENTIALS IN INTACT NEURONAL CIRCUITS

描述 摘要 要破解大脑如何处理感官信息并做出行为决定，最终需要同时记录局部回路中所有神经元的方法。在用于测量神经元活动的技术中，光学显微镜是为数不多的具有在厚组织中进行密集集合记录所需的空间分辨率的工具之一。最近，在开发用于使用荧光测量神经元活动的探针和仪器方面已经取得了重大进展。然而，对于神经回路的研究，这种策略从根本上受到荧光团的光毒性的限制：研究回路所需的长期高速成像提供了损害（并最终破坏）荧光标记细胞的光剂量。为了克服这个问题，我建议开发新的方法来测量扣球活动没有荧光。我们将开发的方法将以足以每秒数千次成像大型三维体积的完整组织的速度执行，足够灵敏以记录每个动作电位，并且足够无损伤地记录同一组神经元数小时。这一技术进步将为神经元活动如何产生大脑的中央计算功能提供前所未有的视角。 公共卫生相关性 该项目将开发一种新的非侵入性方法来记录大脑活动。该技术的一个直接应用将是神经外科，在切除肿瘤或致癫痫组织期间，它可用于快速局部诊断。 以下简历部分由科学审查干事编写，概述了审查委员会就以下问题进行讨论的结果。 脊椎动物（简历）：可接受 委员会的预算建议： 预算是按要求提出的。 科学审查官员注意到： 由于NIH主任先锋奖申请的审查方式不同，

DESCRIPTION Abstract Deciphering how the brain processes sensory information and makes behavioral decisions ultimately requires methods to record simultaneously from all the neurons in a local circuit. Of techniques used to measure neuronal activity, optical microscopy stands out as one of the few tools with the spatial resolution needed for dense ensemble recordings in thick tissue. Recently, significant progress has been made in developing probes and instrumentation for measuring neuronal activity using fluorescence. For studies of neural circuits, however, this strategy is fundamentally limited by the phototoxicity of the fluorophore: long-term, high-speed imaging needed to study circuits delivers a light dose that damages (and ultimately destroys) fluorescently-labeled cells. To overcome this problem, I propose to develop new approaches to measure spiking activity without fluorescence. The methods we will develop will perform at speeds sufficient to image large three-dimensional volumes of intact tissue thousands of times per second, sensitive enough to record each action potential, and sufficiently non-damaging to record from the same set of neurons for periods of hours. This technical advance will provide an unprecedented look at how neuronal activity generates the central computational functions of the brain. Public Health Relevance This project will develop a new non-invasive method for recording brain activity. One immediate application of the technology will be in neurosurgery, where it could be used for rapid local diagnostics during resections of tumors or epileptogenic tissue. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES. VERTEBRATE ANIMAL (Resume): ACCEPTABLE COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested. SCIENTIFIC REVIEW OFFICERS NOTES: Since the NIH Director's Pioneer Award applications are reviewed differentl