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.

项目概要整个听觉系统的神经元都具有显着的可塑性，使听觉回路能够灵活地适应不断变化的任务要求和环境。灵活的听觉行为是两者之间动态相互作用的结果多个听觉区域，包括上游和下游区域。听觉皮层 (AC) 的调节许多行为因素，包括期望、参与和奖励，都支持这一观点：它是一个中心洞察力。然而，交流电并不能孤立地接收来自额叶运动皮层的直接自上而下的输入 (M2) 和来自听觉丘脑 (MGB) 的自下而上的输入形成对听觉很重要的中央听觉轴感知和行为。听觉回路的规范观点专门关注经典反应神经元的作用。因此，具有高度可变的试验放电模式的非经典反应神经元通常被尽管几十年来已被广泛报道，但仍被排除在分析之外。因此，非经典反应神经元促进听觉处理、感知和行为的机制尚不清楚。目标该提案的目的是直接研究由不同系综组成的 AC 中的局部电路如何与下游和上游听觉大脑区域灵活地控制听觉行为。我们将秉持公正、通过考虑整个经典到非经典响应神经元的包容性方法，听觉感知和学习。我们将记录成年小鼠 AC (Aim1) 的尖峰和突触反应，从 AC 和额叶运动皮层的听觉域（M2；目标 2）同时记录，并记录尖峰学习期间听觉丘脑（vMGB；目标 3）的反应并进行光遗传学实验以揭示知觉学习涉及的突触机制和网络动力学。这些实验将提供对灵活听觉行为的神经基础的独特见解，并有助于识别新的治疗靶点改善听力障碍。