Thalamic Modulation of Auditory Cortical Processing via LP

项目摘要 在这个RO 1更新应用中，我们将探索高级丘脑核的功能作用， 外侧后核（LP），在听觉皮层处理。LP是啮齿动物的同源物 枕核虽然以前的研究大多集中在枕的参与， 在视觉功能中，LP/枕和听觉皮层之间存在显著的联系， 提示LP/枕区也可能参与听觉信息处理。 然而，我们对LP如何影响皮层中的听觉处理的知识是缺乏的。 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 在清醒小鼠的初级听觉皮层（A1）的反应。这促使我们提议 一项广泛的调查，以功能的贡献，LP的听觉皮层处理， A1.在目标1中，我们将从颗粒上和颗粒下的单个神经元进行体内记录， A1颗粒层的清醒小鼠，并检查他们的听觉反应特性之前， 在LP的光遗传学失活和活化之后。我们将检验LP扮演一个角色的假设， 通过环境抑制机制增强A1的听觉处理。在Aim中 2、我们将特异性地操纵LP至A1轴突终末的活性， 或化学发生学，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A1反应的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 上级丘（SC），我们将测试的假设，SC-LP-A1途径介导的， 自下而上抑制性调节A1反应。此外，它还可以介导一种跨- 视觉信号对A1反应的模态调制。总之，这些实验将提高 我们对非初级感觉丘脑核团的功能作用的理解。

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.