Understanding how cortex supports flexible sensory representations

项目摘要 学习是大脑的一项基本功能：感觉表征必须灵活，以适应 环境要求和体验，从而使我们能够适应我们周围的世界。了解 学习机制不仅对大脑的正常功能很重要，而且对疾病也很重要，例如， 在单侧听力丧失后。一个重要但经常被忽视的学习原则是 来自其他大脑区域的反馈。在这项资助中，我建议研究皮质分离反馈的功能，从 听觉皮层(ACX)到下丘(IC)，在单侧听力损失后的声音定位学习中。这就做 测试(1)假设皮质-丘脑反馈的功能是提供有关电流的信息 使用光遗传学和行为的感觉条件；以及(2)假设乙酰胆碱(ACh)在 ACX在学习过程中调节IC的活动，使用纤维光度法记录ACX和ACX中ACh的释放动力学 IC的神经活动同时发生。在独立阶段，我将检验(3)假设中的突发活动 从ACX到IC的反馈包含一个错误信号，该信号指导IC的可塑性并导致行为适应 在ACX和IC中使用电生理学和光标记的新收听环境。了解 大脑补偿感觉输入变化的机制可以提供关于如何 最好地开发治疗方法，如听力和其他感官辅助，或为符合以下条件的患者进行感知训练 经历这样的损失，从而提高他们的沟通能力和生活质量。

Project Summary Learning is a fundamental function of the brain: sensory representations must be flexible to adjust to changes in environmental demands and experience, thus allowing us to adapt to the world around us. Understanding the mechanisms of learning are important not only for normal function of the brain but also in disease, for example, after unilateral hearing loss. One important but often overlooked principle of learning is the importance of feedback from other brain areas. In this grant I propose to investigate the function of corticofugal feedback, from auditory cortex (ACx) to inferior colliculus (IC), in sound localization learning after unilateral hearing loss. I will test (1) the hypothesis that the function of cortico-collicular feedback is to provide information about the current sensory conditions using optogenetics and behavior; and (2) the hypothesis that acetylcholine (ACh) release in ACx modulates activity in IC during learning, using fiber photometry to record ACh release dynamics in ACx and neural activity in IC simultaneously. In the independent phase, I will test (3) the hypothesis that burst activity in feedback from ACx to IC contains an error signal which directs plasticity in IC and leads to behavioral adaptation to the new listening environment using electrophysiology and opto-tagging in ACx and IC. Understanding the mechanisms by which the brain compensates for changes in sensory input can provide information about how to best develop treatments, such as hearing and other sensory aids, or perceptual training for patients who experience such losses, thus improving their ability to communicate and quality of life.