Mesoscale bidirectional two-photon holographic optogenetics

点击翻译按钮获取中文摘要

PROJECT SUMMARY Achieving a detailed understanding of the neural codes of sensation, action, and cognition requires technologies that can causally perturb each of the major dimensions of population coding one at a time with extremely high precision across multiple brain areas. Existing control systems do not fully meet this challenge because they are unidirectional and have limited spatial scale, speed, or resolution. To address this need, we will develop an all-optical holographic brain interface that can precisely and bidirectionally alter neural population activity across large volumes of tissue and with extremely high speed. We will build and validate a two-color two-photon holographic microscope and mesoscope and optimize single transcript bidirectional optogenetic tools. Leveraging a new form of ultra-fast sequential holographic illumination, we will obtain cellular-scale, independent bidirectional control over the spiking of hundreds to thousands of neurons across millimeters of brain tissue. Finally, we will develop online approaches that use this new system to precisely and selectively manipulate endogenous interneuronal correlations, neural spike timing, and tuning one at a time. This new technology will allow neuroscientists to distinguish which features of the neural code are causal in neural computation and behavior and which are merely incidental.