WATCHING ACTION POTENTIALS IN INTACT NEURONAL CIRCUITS

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。用于测量 神经元活动，光学显微镜脱颖而出，作为为数不多的工具与所需的空间分辨率， 在厚组织中的密集集合记录。近年来，在开发探针方面取得了重大进展 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， 这种策略从根本上受到荧光团的光毒性的限制：长期、高速成像 研究电路所需的光剂量会破坏（并最终破坏）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尖峰活动， 荧光。我们将开发的方法将以足够的速度对大型三维图像进行处理。 每秒数千次的完整组织体积，灵敏度足以记录每个动作电位，以及 对同一组神经元进行几个小时的无损伤记录。这种技术进步 将提供一个前所未有的看神经元活动如何产生中央计算功能， 大脑

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.