NeuroNex Innovation Award: Chemical and Genetic Methods to Measure and Manipulate Neurons with Light

了解人类大脑仍然是现代科学的重大挑战之一。理解大脑结构和功能所需的学科范围--化学、分子生物学、结构生物学、生物物理学、电子工程、计算科学、认知科学和心理学--更不用说受这种理解影响的探究和探索领域，如宗教、艺术、音乐、哲学、社会学和文学，影响深远。人类大脑中包含的细胞的绝对规模，考虑到大量的神经元，大约800亿，以及每个神经元与其他神经元形成的数百到数千个连接，沿着额外的800亿非神经元支持细胞，使得一个令人生畏的零件清单目录。然而，除了这些不同细胞排列成整体和网络的静态画面之外，这些细胞之间的动态信息流，以及支撑人类存在本质的电和化学脉冲-感觉，思想，情感，认知-不仅代表了复杂性的另一层，而且，在其核心，一个有待解开和探索的深层奥秘。要在这一前沿领域取得进展，需要新的思想、新的工具、新的技术和新的解释，这些几乎肯定会来自跨学科的科学家团队，他们将带来比各部分总和更好的新方法。该项目将开发和应用非侵入性测量脑细胞通信电信号的新方法。该奖项在加州大学伯克利分校建立了NeuroNex创新项目，该项目将开发化学遗传学方法，以非侵入性、高通量、高保真的方式在多个长度尺度上高速测量神经元活动，并以分子精度在多个物种中测量神经元活动。 该团队将通过明亮，敏感，化学合成的电压敏感荧光团直接成像膜电压的变化来光学读出神经元活动。电压敏感荧光团利用光诱导电子转移（PeT）作为电压敏感触发器，在神经元中提供快速，灵敏，非破坏性的光学记录。在该项目中，将基于PetT的电压敏感染料与遗传靶向方法配对，以在完整的动物大脑中实现亚细胞和亚毫秒分辨率的光学电压传感。NeuroNex创新奖是BRAIN Initiative和NSF了解大脑活动的一部分。

Understanding the human brain remains one of the great challenges of modern science. The scope of disciplines required to understand brain structure and function - chemistry, molecular biology, structural biology, biophysics, electrical engineering, computational science, cognitive science and psychology - to say nothing of the fields of inquiry and exploration that are influenced by this understanding, such as religion, art, music, philosophy, sociology and literature, is far-reaching. The sheer scale of the cells contained in the human brain, in contemplating the vast number of neurons, some 80 billion, and the hundreds to thousands of connections that each neuron forms with other neurons, along with the additional 80 billion non-neuronal support cells, makes for a daunting parts list to catalog. And yet, beyond just a static picture of the arrangement of these various cells into ensembles and networks, the dynamic information flow between these cells, the electrical and chemical impulses that underpin the very essence of human existence - sensation, thought, emotion, cognition - represent not just an additional layer of complexity, but, at its core, a deep mystery to be unraveled and explored. To push back at this frontier requires new thoughts, new tools, new techniques, and new interpretations that will almost certainly come from teams of scientists working across disciplines to bring new approaches that are more than the sum of their parts. This project will develop and apply new methods for non-invasively measuring electrical signals underlying brain cell communication.This award establishes a NeuroNex Innovation Project at the University of California, Berkeley, which will develop chemical-genetic methods to measure neuronal activity in a non-invasive, high-throughput, high-fidelity manner across multiple length scales, at high speed, and in multiple species with molecular precision. The team will optically read-out neuronal activity by directly imaging changes in membrane voltage with bright, sensitive, chemically-synthesized voltage-sensitive fluorophores. The voltage-sensitive fluorophore make use of photoinduced electron transfer (PeT) as a voltage-sensing trigger to provide fast, sensitive, non-disruptive optical recordings in neurons. In this project, pairing of PeT-based voltage-sensitive dyes with genetic targeting methods to enable optical voltage sensing with sub-cellular and sub-millisecond resolution in intact animal brains will be conducted. This NeuroNex Innovation Award is part of the BRAIN Initiative and NSF's Understanding the Brain activities.