Functions of locus coeruleus norepinephrine neurons in decision making across multiple timescales

蓝斑去甲肾上腺素神经元在多个时间尺度决策中的功能

基本信息

批准号：
10656752
负责人：
Jeremiah Yaacov Cohen
金额：
$ 226.85万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2023-05-15 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10656752
关键词：
Action Potentials Address Anxiety Area Arousal Attention Attention deficit hyperactivity disorder Axon Behavior Behavioral Brain Calcium Complex Decision Making Diameter Disease Electrophysiology (science)Environment Future Goals Human Individual Influentials Knowledge Learning Link Literature Location Mammals Measurement Measures Mental Depression Moods Motor Motor Cortex Movement Mus Neocortex Neurology Neuromodulator Neurons Norepinephrine Outcome Pattern Pharmaceutical Preparations Play Policies Pontine structure Population Prefrontal Cortex Probability Psychiatry Psychological reinforcement Publishing Pupil Rewards Role Schedule Sensory Series Signal Transduction Tactile Techniques Telencephalon Testing Therapeutic Time Tongue Update Work experience experimental study flexibility learning outcome locus ceruleus structure millisecond neocortical nerve supply neurophysiology neurotransmission neurotransmitter release orofacial programs response sensory feedback sensory input theories

项目摘要

SUMMARY Norepinephrine (NE) is a neurotransmitter released by a small number of neurons in the locus coeruleus (LC), with extensive innervation of the neocortex. Prior work in humans and other mammals led to the hypothesis that LC-NE neurons modulate multiple forms of decision making. This proposal aims to test this overall hypothesis by studying LC-NE neurons in mice performing multiple decision-making tasks. The behaviors to be studied include two types of flexible decision making: how to learn from reinforcement over tens of seconds to minutes in a dynamic choice task and how to rapidly change a motor program based on sensory feedback over hundreds of milliseconds to seconds. The goal of the project is to link action potentials from identified LC-NE neurons to both types of behavior, and determine how large populations of neurons in multiple cortical areas are modulated by NE input to achieve flexible behavior. Three aims test three hypothesis that address different mechanistic questions about the functions of norepinephrine in neocortex: 1) LC-NE neurons modulate reinforcement learning during a dynamic choice task; 2) norepinephrine regulates sensory-driven motor program switching; 3) LC-NE modulates orofacial and prefrontal cortex for effective reinforcement learning and motor program switching. Measurements and manipulation (activation and inactivation) of the activity of NE neurons and their targets in neocortex, during well-controlled behavioral tasks in mice, will enable testing these three hypotheses. Understanding the spatial and temporal dynamics of NE release in cortex will be necessary for understanding flexible decision making in general, and disorders of attention, arousal, and mood that rely on its function.

概括去甲肾上腺素（NE）是由少数神经元（LC）中的少数神经元释放的神经递质随着新皮层的广泛神经支配。人类和其他哺乳动物的先前工作导致了假设 LC-NE神经元调节了多种形式的决策。该建议旨在测试这一总体通过研究执行多个决策任务的小鼠中的LC-NE神经元的假设。行为是研究包括两种灵活的决策：如何在数十秒内从增强中学习动态选择任务的分钟以及如何基于感觉反馈来快速更改电动机程序数百毫秒到几秒钟。该项目的目的是将已确定的LC-NE的动作电位联系起来神经元对两种类型的行为，并确定多个皮质区域的神经元群通过NE输入调节以实现灵活的行为。三个目标测试三个假设，解决了有关功能的不同机械问题新皮层中的去甲肾上腺素：1）LC-NE神经元在动态选择任务中调节增强学习； 2）去甲肾上腺素调节感官驱动的电机程序切换； 3）LC-NE调节口面和有效增强学习和运动程序切换的前额叶皮层。测量和 NE神经元活动及其在新皮层中的活性的操纵（激活和灭活），期间在小鼠中控制良好的行为任务将实现这三个假设的测试。了解空间对于理解柔性决策，需要依赖其功能的一般关注，唤醒和情绪的疾病。