The role of noradrenaline in signaling prediction error and promoting learning

去甲肾上腺素在信号预测错误和促进学习中的作用

• 批准号: RGPIN-2019-06947
• 负责人: Corbit, Laura
• 金额: $ 2.91万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716530
• 关键词: role; noradrenaline; signaling; prediction; error

Predictive learning is highly adaptive; it allows us and other animals to use information in the environment to anticipate and prepare for biologically significant events. Equally important is the ability to update previous learning when environmental conditions change, and the organism's predictions about impending events are no longer accurate. This project examines the role of the neurotransmitter noradrenaline (NA) in this particular form of error-driven learning. Detecting and encoding relationships between events and, in particular, modifying previous learning when confronted with new information is essential for adaptive, flexible control of behaviour. However, we still know very little about the neural systems that make this possible. While substantial research implicates dopamine (DA) in initial learning about rewarding events, recent research conducted by Dr. Corbit has shown that updating this learning, notably in extinction (when expected reinforcement is omitted), involves noradrenaline (NA). Critical questions remain regarding the broader role of NA in in signaling reward prediction errors and how this activity translates into new learning. This research program will adopt a multidisciplinary approach. We will use a battery of sophisticated behavioural tasks specifically designed to manipulate prediction error. These behavioural methods will be combined with state of the art neuroscience methods that record (in vivo electrophysiology) and manipulate (optogenetics; pharmacological treatments) neural activity during ongoing behavioural tasks with temporal and spatial precision unsurpassed by other methods to define the role of NA in signaling prediction error and driving learning. This work will be of wide interest because it addresses basic questions about motivation, arousal and reinforcement learning. This project is significant because establishing and updating knowledge about the relationship between events in the world is a fundamental capacity essential for adaptive behaviour and failure to flexibly modify previously learned responses is central to a number of neuropsychiatric diseases including dementia, depression, drug addiction and attention deficit hyperactivity disorder (ADHD). To understand pathology of this kind requires insight into the neural bases of learning and attention in the healthy brain. If NA plays a major role in either error-driven learning in general or specifically in the updating of learning when conditions change, then this has major implications for our conception of the neurobiology of learning. In addition, this research program provides a multidisciplinary training environment, with specified roles for postdoctoral fellows, graduate students and undergraduate students and numerous opportunities for trainees to develop a wide range of research skills from the conception of the question and hypothesis, design of experiments, to data collection and interpretation, and finally manuscript preparation.

预测学习具有高度的适应性，它允许我们和其他动物利用环境中的信息来预测和准备生物学上的重大事件。同样重要的是，当环境条件发生变化时，生物体对即将发生的事件的预测不再准确时，更新先前学习的能力。这个项目研究了神经递质去甲肾上腺素（NA）在这种特殊形式的错误驱动学习中的作用。检测和编码事件之间的关系，特别是当遇到新的信息时，修改以前的学习对于自适应，灵活的行为控制至关重要。然而，我们仍然对使这成为可能的神经系统知之甚少。虽然大量的研究表明多巴胺（DA）参与了对奖励事件的初始学习，但Corbit博士最近进行的研究表明，更新这种学习，特别是在灭绝（当预期的强化被省略时），涉及去甲肾上腺素（NA）。关于NA在信号奖励预测错误中的更广泛作用以及这种活动如何转化为新的学习，仍然存在关键问题。 该研究计划将采用多学科方法。我们将使用一组专门设计用于操纵预测误差的复杂行为任务。这些行为方法将与最先进的神经科学方法相结合，这些方法记录（体内电生理学）和操纵（光遗传学;药理学治疗）正在进行的行为任务期间的神经活动，其时间和空间精度无法被其他方法超越，以定义NA在信号预测错误和驱动学习中的作用。 这项工作将引起广泛的兴趣，因为它解决了有关动机，唤醒和强化学习的基本问题。这个项目意义重大，因为建立和更新关于世界上各种事件之间关系的知识是适应行为所必不可少的一种基本能力，而不能灵活地修改以前学到的反应是包括痴呆症、抑郁症、吸毒成瘾和注意力缺陷多动障碍在内的一些神经精神疾病的核心。要理解这种病理学，需要深入了解健康大脑中学习和注意力的神经基础。如果NA在错误驱动的学习中起着重要作用，或者在条件改变时，NA在学习更新中起着重要作用，那么这对我们的学习神经生物学概念有重要意义。此外，该研究计划提供了一个多学科的培训环境，为博士后研究员，研究生和本科生提供了特定的角色，并为学员提供了许多机会，以培养广泛的研究技能，从问题和假设的概念，实验设计，到数据收集和解释，最后是手稿准备。