Thalamic Modulation of Auditory Cortical Processing via LP

通过 LP 进行听觉皮层处理的丘脑调节

• 批准号: 10238062
• 负责人: Li I Zhang
• 金额: $ 55.4万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238062
• 关键词: Address; Affect; Anatomy; Area; Auditory; Auditory area; Axon; Behavioral; Brain; Cell Nucleus; Coupled; Discrimination; Frequencies; Grant; Homologous Gene; Individual; Investigation; Knowledge; Lateral posterior nucleus of thalamus; Mediating; Modality; Mus; Nature; Neural Pathways; Neurons; Noise; Pathway interactions; Performance; Pharmacology; Play; Preparation; Presynaptic Terminals; Primates; Property; Pulvinar structure; Research; Rodent; Role; Sensory; Signal Transduction; Slice; Stratum Granulosum; Synapses; Testing; Thalamic Nuclei; Thalamic structure; Viral; Vision; Visual; Whole-Cell Recordings; auditory discrimination; auditory pathway; auditory processing; awake; base; cell type; experimental study; hippocampal pyramidal neuron; in vivo; individual response; information processing; inhibitory neuron; insight; multisensory; neural circuit; optogenetics; receptive field; response; sensory cortex; sensory processing disorder; sound; superior colliculus Corpora quadrigemina; visual processing

Project Summary In this RO1 renewal application, we will explore functional roles of a higher-order thalamic nucleus, the lateral posterior nucleus (LP), in auditory cortical processing. LP is a rodent homologue of the pulvinar nucleus. While previous studies have been mostly focused on involvements of pulvinar in visual functions, there are salient connections between LP/pulvinar and auditory cortex, suggesting potential involvements of LP/pulvinar in auditory information processing as well. However, our knowledge on how LP influences auditory processing in the cortex is lacking. Recently in our preliminary experiments we observed that LP activity could suppress auditory responses in the primary auditory cortex (A1) of awake mice. This has prompted us to propose an extensive investigation into the functional contribution of LP to auditory cortical processing in A1. In Aim 1, we will perform in vivo recordings from individual neurons in supragranular and granular layers of A1 in awake mice and examined their auditory response properties before and after optogenetically inactivation and activation of LP. We will test the hypothesis that LP plays a role in enhancing auditory processing in A1 through a surround-suppression mechanism. In Aim 2, we will specifically manipulate the activity of the LP to A1 axon terminals either optogenetically or chemogenetically, and examine A1 neuron cell types that are innervated by the LP-A1 projection. We will test the hypothesis that the LP modulation of A1 responses is primarily mediated by the LP projection to layer 1 inhibitory neurons. In Aim 3, by manipulating activity of superior colliculus (SC), we will test the hypothesis that a SC-LP-A1 pathway mediates the bottom-up suppressive modulation of A1 responses. In addition, it can also mediate a cross- modality modulation of A1 responses by visual signals. Together, these experiments will enhance our understanding of functional roles of non-primary sensory thalamic nuclei in general.

项目概要 在这个 RO1 更新应用中，我们将探索高阶丘脑核的功能作用， 外侧后核 (LP)，参与听觉皮层处理。 LP 是啮齿动物的同系物 枕核。虽然之前的研究主要集中在枕丘的参与上 在视觉功能中，LP/枕丘和听觉皮层之间存在显着的联系， 表明 LP/pulvinar 也可能参与听觉信息处理。 然而，我们对 LP 如何影响皮层听觉处理的了解还很缺乏。 最近，在我们的初步实验中，我们观察到 LP 活动可以抑制听觉 清醒小鼠初级听觉皮层（A1）的反应。这促使我们提出 对 LP 对听觉皮层处理的功能贡献的广泛研究 A1。在目标 1 中，我们将对颗粒上和颗粒中的单个神经元进行体内记录。 清醒小鼠中 A1 的颗粒层，并在之前和之后检查了它们的听觉反应特性 LP 光遗传学失活和激活后。我们将检验 LP 扮演一个角色的假设 通过环绕抑制机制增强 A1 听觉处理的作用。瞄准 2，我们将通过光遗传学专门操纵 LP 到 A1 轴突末端的活动 或化学遗传学，并检查由 LP-A1 神经支配的 A1 神经元细胞类型 投影。我们将检验以下假设：A1 响应的 LP 调制主要是 由 LP 投射到第 1 层抑制性神经元介导。在目标 3 中，通过操纵 上丘（SC），我们将检验 SC-LP-A1 通路介导的假设 A1 反应的自下而上抑制调节。此外，它还可以调解跨 视觉信号对 A1 反应的模态调节。这些实验共同将增强 我们对非初级感觉丘脑核团功能作用的总体理解。