WATCHING ACTION POTENTIALS IN INTACT NEURONAL CIRCUITS

描述 摘要 要破译大脑如何处理感觉信息和做出行为决定，最终需要从局部电路中的所有神经元同时进行记录的方法。在用于测量神经元活动的技术中，光学显微镜脱颖而出，成为少数几种具有空间分辨率的工具之一，这些工具需要在厚组织中进行密集的整体记录。近年来，在利用荧光技术测量神经元活动的探针和仪器方面取得了重大进展。然而，对于神经电路的研究，这一策略从根本上受到了荧光团的光毒性的限制：研究电路所需的长期、高速成像提供的光剂量会损害(并最终摧毁)荧光标记的细胞。为了克服这个问题，我建议开发新的方法来测量无荧光的尖峰活动。我们将开发的方法将以足以每秒数千次成像大型完整组织的三维体积的速度执行，足够灵敏来记录每个动作电位，并且足够无损伤地从同一组神经元记录几个小时。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一个前所未有的视角。 公共卫生相关性 该项目将开发一种新的非侵入性记录大脑活动的方法。这项技术的一个直接应用将是神经外科，在肿瘤或致痫组织切除过程中，它可以用于快速局部诊断。 科学审查干事编写了以下简历部分，以总结审查委员会关于下列问题的讨论结果。 脊椎动物(简历)：可以接受 委员会预算建议： 预算是按要求建议的。 科学审查官员指出： 由于NIH主任先锋奖的申请受到不同的审查

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