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: 10466838
• 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/10466838
• 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.

项目摘要 在此RO1更新应用中，我们将探索高阶丘脑核的功能作用， 侧后核（LP），在听觉皮质加工中。 LP是啮齿动物的同源物 pulvinar核。虽然先前的研究主要集中在pulvinar的参与上 在视觉功能中，LP/Pulvinar和听觉皮层之间存在显着连接， 也暗示了LP/Pulvinar在听觉信息处理中的潜在参与。 但是，我们缺乏有关LP如何影响皮质中听觉处理的知识。 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 醒着小鼠的主要听觉皮层（A1）中的反应。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AIM 1中，我们将从上部的单个神经元和 A1在清醒小鼠中的颗粒层，并检查了其听觉响应属性 在光遗传学失活和LP激活后。我们将测试LP扮演的假设 通过环绕抑制机制增强A1中听觉处理的作用。目标 2，我们将专门操纵LP对A1轴突终端的活性。 或化学上，检查由LP-A1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投影介导的1层抑制神经元。在AIM 3中，通过操纵活动 上丘（SC），我们将检验以下假设：SC-LP-A1途径介导 自下而上的抑制A1响应调节。此外，它还可以介导一个交叉 通过视觉信号对A1响应的模态调节。这些实验将共同增强 我们对一般的非主要感觉丘脑核的功能作用的理解。