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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的感知引导的行为涉及外部输入和外部输入之间复杂且动态的相互作用。例如，与警觉性、动机、期望和注意力相关的内部状态。范围广泛大量证据表明灵长类动物大脑中感觉信息的表示、处理和流动受多种神经调节系统的调节。然而，我们对生理和神经调节信号在灵长类动物复杂行为过程中的行为影响是相当初级的，落后于啮齿类动物的已知水平。造成这种滞后的主要原因是缺乏先进的分子、用于靶向神经调节回路并研究其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。当前提案的总体目标是开发和测试用于监测的光遗传工具箱控制清醒、有行为的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质回路产生强大但人们知之甚少的影响调解感知决策。为了实现这一目标，我们将使用先进的解剖学和转录组学工具来识别主要的可能在控制信息中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层区域的处理和流动。接下来我们将开发基于病毒的遗传工具，将允许人们选择性地表达这些关键的报告者和执行者灵长类动物的神经调节回路。最后，我们将开发和优化光学和电生理学允许人们在测量的同时监视和控制神经调节电路的工具当猴子执行复杂的感知任务时，关键皮层区域的神经群体反应精确控制的行为要求。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知觉决策过程中。该光遗传学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性行为中的作用。更一般地说，将开发用于监测和操纵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期间神经信息处理的能力。