An optical-genetic toolbox for monitoring and controlling diverse neuromodulatory circuits governing complex behaviors in primates

用于监测和控制灵长类动物复杂行为的多种神经调节回路的光遗传工具箱

• 批准号: 10650669
• 负责人: Karl A. Deisseroth
• 金额: $ 134.24万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650669
• 关键词: Adaptive Behaviors; Anatomy; Animal Model; Attention; Behavior; Behavioral; Brain; Brain region; Cognition; Complex; Decision Making; Electrophysiology (science); Genetic; Goals; Human; Measures; Mediating; Methods; Molecular; Monitor; Monkeys; Motivation; Motor; Neuromodulator; Optics; Perception; Performance; Physiological; Play; Population; Primates; Reporter; Rodent; Role; Sensory; Signal Transduction; System; Testing; Viral; alertness; awake; expectation; information processing; motor control; neural; neural information processing; neuropathology; neuroregulation; nonhuman primate; response; selective expression; tool; transcriptomics

ABSTRACT Perceptually guided behavior involves a complex and dynamic interplay between external inputs and internal states that are related, for example, to alertness, motivation, expectations and attention. A wide range of evidence suggests that the representation, processing, and flow of sensory information in the primate brain is regulated by several neuromodulatory systems. However, our understanding of the physiological and behavioral impact of neuromodulatory signals during complex behaviors in primates is quite rudimentary and is lagging behind what is known in rodents. The main reason for this lag is the lack of advanced molecular, genetic and physiological tools for targeting neuromodulatory circuits and for studying their role in behaving non-human primates, which are the best animal model for human perception, cognition and motor control. The overarching goal of the current proposal is to develop and test an optical-genetic toolbox for monitoring and controlling multiple interacting brain regions in awake, behaving non-human primates. We focus on neuromodulatory circuits that exert a powerful, yet poorly understood, impact on the cortical circuits that mediate perceptual decision-making. To achieve this goal, we will use advanced anatomical and transcriptomic tools to identify the main neuromodulatory molecules and circuits that are likely to play an important role in controlling information processing and flow in several key cortical regions along the sensory-decision-motor arc. We will then develop viral-based genetic tools that will allow one to selectively express reporters and actuators in these key neuromodulatory circuits in primates. Finally, we will develop and optimize optical and electrophysiological tools that will allow one to monitor and control neuromodulatory circuits while simultaneously measuring neural population responses in key cortical regions as monkeys perform complex perceptual tasks with precisely-controlled behavioral demands. To validate these methods, we will study the role of neuromodulators during perceptual decision-making in primates. This optical-genetic toolbox will be widely applicable for studying the role of neuromodulatory circuits in mediating adaptive behaviors in primates. More generally, the tools that will be developed for monitoring and manipulating multiple interacting brain regions during behavior will advance our ability to study neural information processing during complex behaviors in primates.

摘要 感知引导行为涉及外部输入和外部输入之间复杂而动态的相互作用 例如，与警觉性、积极性、期望值和注意力相关的内部状态。范围很广 证据表明，灵长类动物大脑中感觉信息的表示、处理和流动 受到几个神经调节系统的调节。然而，我们对生理和心理的理解 在灵长类动物的复杂行为中，神经调节信号对行为的影响是非常初级的和 落后于已知的啮齿动物。造成这种滞后的主要原因是缺乏先进的分子， 以神经调节回路为靶点并研究它们在行为中的作用的遗传和生理工具 非人灵长类动物是人类感知、认知和运动控制的最佳动物模型。 当前提议的首要目标是开发和测试用于监测的光学遗传工具箱 以及控制清醒的、表现为非人类灵长类动物的多个相互作用的大脑区域。我们专注于 神经调节回路对皮层回路施加强大但知之甚少的影响 调解感性决策。 为了实现这一目标，我们将使用先进的解剖学和转录学工具来识别主要的 可能在控制信息方面发挥重要作用的神经调节分子和电路 沿着感觉-决策-运动弧的几个关键皮质区域的加工和流动。然后我们将开发出 基于病毒的基因工具，将允许人们在这些关键字中选择性地表达记者和致动器 灵长类动物的神经调节回路。最后，我们将发展和优化光学和电生理 允许人们在同时测量的同时监测和控制神经调节电路的工具 猴子执行复杂的知觉任务时，关键皮质区域的神经群反应 精确控制的行为需求。为了验证这些方法，我们将研究神经调节剂的作用。 在灵长类动物的感性决策过程中。这种光学遗传工具箱将广泛应用于 研究神经调节回路在调节灵长类动物适应行为中的作用。更广泛地说， 将开发用于监控和操作多个相互作用的大脑区域的工具 行为将提高我们研究灵长类动物复杂行为中神经信息处理的能力。