The significance of nominally non-responsive neural dynamics in auditory perception and behavior

名义上无反应的神经动力学在听觉感知和行为中的意义

基本信息

批准号：
10677342
负责人：
Michele Insanally
金额：
$ 44.02万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2023-04-10 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677342
关键词：
Acoustics Adult Animals Area Auditory Auditory Perception Auditory area Auditory system Behavior Behavioral Brain Brain region Cells Central Auditory Processing Disorder Communication Cues Development Devices Diagnosis Dimensions Disease Electrophysiology (science)Environment Exclusion Frequencies Goals Hearing problem Injury Language Development Language Disorders Learning Learning Disorders Measures Motor Cortex Mus Neurons Pathway interactions Patients Pattern Perception Perceptual learning Phase Physiological Prevalence Process Property Publishing Reporting Reversal Learning Rewards Role Sensory Shapes Stimulus Synapses Synaptic plasticity Task Performances Techniques Testing Thalamic structure Work auditory processing auditory thalamus computerized tools deaf density developmental disease expectation experience experimental study flexibility hearing impairment hearing restoration improved in vivo insight learning outcome neural neural circuit neuroprosthesis new therapeutic target next generation novel optogenetics recruit response sensory gating sensory input sound targeted treatment

项目摘要

Project Summary Neurons throughout the auditory system are remarkably plastic, allowing auditory circuits to flexibly adapt to changing task demands and context. Flexible auditory behavior is the result of a dynamic interaction between several auditory regions including upstream and downstream areas. The auditory cortex (AC) is modulated by many behavioral factors including expectation, enagagement, and reward supporting the view that it is a hub for perception. However, AC does not operate in isolation receiving direct top-down inputs from frontal-motor cortex (M2) and bottom-up inputs from auditory thalamus (MGB) forming a central auditory axis important for auditory perception and behavior. The canonical view of auditory circuits has exclusively focused on the role of classically responsive neurons. Thus, non-classically responsive neurons with highly variable trial-to-trial firing patterns have typically been excluded from analysis despite being widely reported for decades. Thus, the mechanisms by which non-classically responsive neurons contribute to auditory processing, perception, and behavior is unclear. The goal of this proposal is to directly investigate how local circuits in AC comprised of diverse ensembles interact with downstream and upstream auditory brain regions to flexibly gate auditory behavior. We will take an unbiased, inclusive approach by considering the entire spectrum of classically to non-classically responsive neurons, to auditory perception and learning. We will record spiking and synaptic responses from adult mouse AC (Aim1), record simultaneously from AC and an auditory domain of frontal-motor cortex (M2; Aim 2), and record spiking responses from auditory thalamus (vMGB; Aim 3) during learning and perform optogenetic experiments to reveal synaptic mechanisms and network dynamics involved in perceptual learning. These experiments will provide unique insight into the neural basis of flexible auditory behaviors, and help identity novel therapeutic targets for improving hearing disorders.

项目摘要整个听觉系统中的神经元非常塑料，使听觉电路可以灵活地适应改变任务需求和上下文。灵活的听觉行为是导致动态相互作用的结果几个听觉区域，包括上游和下游区域。听觉皮层（AC）由许多行为因素，包括期望，参与和奖励，支持它是一个枢纽的观点洞察力。但是，AC不会孤立地运行，从额叶运动皮层接收直接自上而下的输入（M2）和自下而上的输入来自听觉的丘脑（MGB），形成了对听觉很重要的中央听觉轴感知和行为。听觉电路的规范观点仅关注经典响应神经元的作用。因此，具有高度可变的试验性触发模式的非传统响应性神经元通常已经存在尽管被广泛报道了数十年，但被排除在分析之外。因此，尚不清楚非经典响应神经元有助于听觉处理，感知和行为的机制。目标该提案的内容是直接研究AC中的本地电路如何由不同的合奏组成下游和上游听觉大脑区域，以灵活地听觉行为。我们将不偏见，通过考虑整个经典的非经典响应神经元的范围，到包容性方法，听觉的感知和学习。我们将记录成年小鼠AC的尖峰和突触反应（AIM1），同时记录AC和额叶皮层的听觉域（M2； AIM 2），并记录尖峰在学习和执行光遗传学实验期间，听觉丘脑的响应（VMGB； AIM 3）以揭示感知学习涉及的突触机制和网络动态。这些实验将提供对灵活的听觉行为的神经基础的独特见解，并帮助身份新颖的治疗目标改善听力障碍。