Thalamic Modulation of Auditory Cortical Processing via LP

项目摘要 在这个RO1更新应用中，我们将探索更高阶丘脑核的功能作用， 听觉皮质加工中的外侧后核(LP)。LP是啮齿类动物的同源物 枕核。虽然以前的研究大多集中在枕骨受累上 在视觉功能方面，Lp/枕叶和听觉皮质之间有显著的联系， 提示Lp/枕区可能参与听觉信息处理。 然而，我们对LP如何影响大脑皮层的听觉处理缺乏了解。 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质(A1)的反应。这促使我们提议 Lp在听觉皮层加工中的功能贡献的广泛研究 A1.在目标1中，我们将从颗粒上和颗粒上的单个神经元进行活体记录 清醒小鼠的A1颗粒层，并检测其听觉反应特性 经过光遗传失活和激活后的LP。我们将测试LP扮演一个 通过环绕抑制机制在A1中增强听觉处理的作用。在AIM 2，我们将专门操纵LP到A1轴突终末的活动 或化学遗传学，并检查由Lp-A1神经支配的A1神经细胞类型 投影。我们将检验A1响应的LP调制主要是 由LP向第1层抑制性神经元的投射介导。在目标3中，通过操纵 上丘(SC)，我们将检验SC-LP-A1通路介导 A1反应的自下而上抑制调制。此外，它还可以调解一个交叉- 视觉信号对A1反应的通道调制。总之，这些实验将增强 我们对丘脑非初级感觉核团的功能作用的总体理解。

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.