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

项目摘要 整个听觉系统中的神经元具有显著的可塑性，使得听觉回路能够灵活地适应 不断变化的任务需求和环境。灵活的听觉行为是 包括上游和下游区域的几个听觉区域。听觉皮层（AC）是由 许多行为因素，包括期望、激励和奖励，支持了它是一个中心的观点。 perception.然而，AC并不孤立地接受来自额叶运动皮层的直接自上而下的输入 (M2)以及来自听觉丘脑（MGB）的自下而上的输入，形成对听觉重要的中枢听觉轴。 感知和行为。 听觉回路的经典观点只关注经典反应神经元的作用。 因此，具有高度可变的试验到试验放电模式的非经典响应神经元通常被认为是 尽管几十年来被广泛报道，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 该建议的目的是直接研究由不同合奏组成的AC中的局部电路如何与 下游和上游听觉大脑区域来灵活地控制听觉行为。我们将采取公正的， 通过考虑经典到非经典反应神经元的整个频谱， 听觉感知和学习。我们将记录成年小鼠AC（Aim 1）的尖峰和突触反应， 同时从AC和额叶运动皮层的听觉域（M2; Aim 2）记录，并记录尖峰 听觉丘脑（vMGB; Aim 3）的反应，并进行光遗传学实验，以揭示 突触机制和网络动力学参与知觉学习。这些实验将提供 对灵活听觉行为的神经基础的独特见解，并帮助确定新的治疗目标， 改善听力障碍。

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.