WATCHING ACTION POTENTIALS IN INTACT NEURONAL CIRCUITS

观察完整神经回路中的动作电位

• 批准号: 8306917
• 负责人: Timothy Holy
• 金额: $ 75.24万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306917
• 关键词: Action Potentials; Behavioral; Brain; Cells; Dose; Fluorescence; Hour; Image; Label; Light; Measures; Methods; Microscopy; Neurons; Optics; Phototoxicity; Resolution; Sensory Process; Speed; Techniques; Thick; Time; Tissues; fluorophore; instrumentation; neural circuit; novel strategies; tool

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.

破译大脑如何处理感官信息并做出行为决策最终需要 同时记录本地电路中所有神经元的方法。用于测量的技术 神经元活动，光学显微镜是少数具有神经元活动所需空间分辨率的工具之一 厚组织中的密集合奏录音。近期，探针研制取得重大进展 以及使用荧光测量神经元活动的仪器。然而，对于神经回路的研究， 该策略从根本上受到荧光团光毒性的限制：长期、高速成像 研究电路所需的光剂量会损坏（并最终破坏）荧光标记 细胞。为了克服这个问题，我建议开发新的方法来测量尖峰活动，而无需 荧光。我们将开发的方法将以足以对大型三维图像进行成像的速度执行 每秒数千次的完整组织体积，足够敏感以记录每个动作电位，以及 足够无损，可以从同一组神经元进行数小时的记录。这项技术进步 将为神经元活动如何产生中央计算功能提供前所未有的视角 大脑。