Mesoscale bidirectional two-photon holographic optogenetics

项目摘要 要想详细了解感觉、动作和认知的神经编码，就需要一些技术，这些技术可以在多个大脑区域中以极高的精度，一次一个地因果干扰群体编码的每个主要维度。现有的控制系统不能完全满足这一挑战，因为它们是单向的，并且具有有限的空间尺度、速度或分辨率。为了满足这一需求，我们将开发一种全光学全息大脑接口，它可以精确地双向改变大量组织中的神经群体活动，并且速度非常快。我们将建立并验证双色双光子全息显微镜和介观镜，并优化单转录本双向光遗传学工具。利用一种新形式的超快顺序全息照明，我们将获得细胞规模的，独立的双向控制数百至数千个神经元在毫米的脑组织中的尖峰。最后，我们将开发在线方法，使用这个新系统来精确和选择性地操纵内源性神经元间的相关性，神经尖峰时间，并调整一个时间。这项新技术将使神经科学家能够区分神经代码的哪些特征在神经计算和行为中是因果关系，哪些只是偶然的。

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.