Closed-Loop Systems for Large Scale Spatiotemporal Imaging and Actuation of Neural Activity in Freely Behaving Animals

用于自由行为动物的大规模时空成像和神经活动激活的闭环系统

• 批准号: 10401560
• 负责人: Daniel Aharoni
• 金额: $ 67.72万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401560
• 关键词: Adoption; Animal Experiments; Animals; Area; Automobile Driving; Behavior; Behavior Control; Behavioral; Brain; Cells; Communities; Complex; Data; Detection; Development; Devices; Educational workshop; Equipment; Event; Feedback; Foundations; Generations; Goals; Grain; Head; Hippocampus (Brain); Image; Investigation; Knowledge; Learning; Light; Lighting; Link; Measures; Memory; Methodology; Microscope; Mus; Neurons; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; Nucleus Accumbens; Operative Surgical Procedures; Optics; Pattern; Persons; Process; Protocols documentation; Rattus; Reading; Research Personnel; Role; Sampling; Site; Slice; Social Interaction; Source Code; Structure; System; Techniques; Technology; Testing; Time; Training; Work; Writing; awake; design; design-build-test; experience; experimental study; image processing; improved; in vivo evaluation; innovation; neural circuit; neural network; neurobehavioral; novel; online resource; open source; open source tool; process optimization; prototype; relating to nervous system; spatiotemporal; tool; wiki

ABSTRACT A major challenge in neuroscience is to uncover how defined neural circuits in the brain encode, store, modify, and retrieve information. Adding to this challenge is the fact that neural function does not operate in isolation but rather within living, behaving animals. Great technological advances over the past decades have allowed researchers to begin to optically measure and modulate neural activity but these approaches are often limited to head-fix animals when studying neural function at spatial and temporal scales relevant to internal neural circuit dynamics. While a great deal of scientific and technological progress has been made, there is still much to learn concerning complex neural function, especially within the context of natural behavior. This knowledge gap, at least in part, is due to a lack of accessible tools for simultaneously modulating and observing large-scale neural circuits with single-cell precision in freely behaving animals. This project will fill this gap by developing open-source, head-mounted miniature microscopes with spatiotemporal illumination capabilities for both patterned photo-stimulation and improved neural imaging in freely behaving animals. We will develop a modular control and acquisition platform for native integration of neural and behavioral equipment to facilitate neural-behavioral experiments. Finally, this platform will be driven by a novel, automated, closed-loop processing framework for detecting, decoding, and manipulating neural and behavioral dynamics in real-time. The goal of this platform is to 1) significantly extend and improve upon current freely behaving neural imaging and modulation techniques and 2) provide an integrated framework for observing, controlling, and manipulating neural dynamics within the context of behavior. This approach has the potential to simultaneously “read” from and “write” into, potentially, any area of the brain, enabling fine-grained investigation of the causal role between neural activity and behavior. Our development will be guided by concurrent benchtop and in vivo testing at every stage of the development and optimization process. To maximize the impact of our efforts, all tools and technologies developed for this proposal will be open-source and shared widely with the scientific community through online resources and technical workshops.

摘要 神经科学的一个主要挑战是揭示大脑中定义的神经回路如何编码，存储，修改和检索信息。增加这一挑战的是，神经功能不是孤立地运作，而是在活着的、有行为的动物体内运作。在过去的几十年里，巨大的技术进步使研究人员开始光学测量和调节神经活动，但这些方法往往局限于头部固定动物在空间和时间尺度上研究神经功能相关的内部神经回路动力学。虽然科学和技术已经取得了很大的进步，但关于复杂的神经功能，特别是在自然行为的背景下，仍然有很多东西需要学习。这种知识差距，至少在一定程度上是由于缺乏可访问的工具来同时调节和观察自由行为动物中具有单细胞精度的大规模神经回路。该项目将通过开发开源的头戴式微型显微镜来填补这一空白，该显微镜具有时空照明能力，可用于图案化光刺激和改善自由行为动物的神经成像。我们将开发一个模块化的控制和采集平台，用于神经和行为设备的本地集成，以促进神经行为实验。最后，该平台将由一个新颖的自动化闭环处理框架驱动，用于实时检测、解码和操纵神经和行为动态。该平台的目标是：1）显著扩展和改进当前自由行为神经成像和调制技术; 2）提供一个在行为背景下观察、控制和操纵神经动力学的集成框架。这种方法有可能同时从大脑的任何区域“读取”和“写入”，从而能够对神经活动和行为之间的因果关系进行细粒度的调查。在开发和优化过程的每个阶段，我们的开发将以并行的实验室和体内测试为指导。为了最大限度地发挥我们的努力的影响，为这项提案开发的所有工具和技术都将是开源的，并通过在线资源和技术研讨会与科学界广泛分享。