Network modulators of auditory thalamocortical feedback inhibition

听觉丘脑皮质反馈抑制的网络调节器

• 批准号: 10227956
• 负责人: Ben D Richardson
• 金额: $ 14.75万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-03 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227956
• 关键词: Achievement; Acoustics; Address; Afferent Neurons; Amygdaloid structure; Anatomy; Area; Arousal; Attention; Auditory; Auditory Perceptual Disorders; Basal Ganglia; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Cells; Cerebellar Nuclei; Cerebellum; Code; Complex; Data; Dendrites; Electrophysiology (science); Emotional; Emotions; Environment; Event; Feedback; Fluorescent in Situ Hybridization; Foundations; Functional disorder; Glutamates; Glycine; Goals; Hippocampus (Brain); Immunohistochemistry; In Situ Hybridization; Investigation; Knowledge; Link; Location; Modeling; Molecular; Mus; Neurons; Neurotransmitter Receptor; Neurotransmitters; Noise; Output; Parvalbumins; Pathway interactions; Perception; Play; Population; Process; Property; Pseudorabies; Reporter; Role; Sensory; Shapes; Somatostatin; Source; Stimulus; Synapses; System; Thalamic Nuclei; Thalamic structure; Time; Tinnitus; Transgenic Organisms; Viral; Whole-Cell Recordings; Work; auditory processing; auditory stimulus; auditory thalamus; autism spectrum disorder; base; cell type; gamma-Aminobutyric Acid; in vivo; inhibitory neuron; insight; multimodality; nervous system disorder; neurotransmitter release; novel; optogenetics; relating to nervous system; sensory processing disorder; signal processing; spatiotemporal

PROJECT SUMMARY/ABSTRACT Accurate coding and filtering of auditory information depends on the auditory thalamocortical circuit, dysfunction of which is linked to tinnitus and Autism Spectrum Disorder (ASD). Within this circuit, the thalamic reticular nucleus influences auditory thalamocortical neuron coding and activity to determine parameters of attention and stimulus selection, but an understanding of this circuit is incomplete. Clearly, thalamic and cortical afferents modulate the thalamic reticular nucleus, but other extrathalamocortical brain regions are also involved in shaping the sensory filtering properties of the TRN. We hypothesize that brain regions which integrate multi- modal sensory information to form internal predictions or determine emotional state are important for ‘tuning’ the filtering properties of TRN neurons through modulation of TRN activity, auditory coding, and sensory selection behaviors. Preliminary data indicate cerebellar output nuclei (sensorimotor predictions) and amygdala (emotion) directly project to the thalamic reticular nucleus – a brain region that inhibits sensory thalamic neurons to modulate stimulus coding, selection, and attention. This direct connection between cerebellum and thalamic reticular nucleus may be an important conduit for the relay of multi-modal sensory information and related predictions about surrounding events in time and space (e.g. changes in multiple acoustic stimuli sources, background noise, etc.). Likewise, a direct projection from the amygdala to the thalamic reticular nucleus may provide emotional context regulating selection of and attention to specific stimuli (e.g. heightened perception in stressful environments). While anatomical evidence for these connections is clear, the function of cerebellar and amygdala projections to thalamic reticular nucleus, cell type-specific circuitry, and subsequent influence on auditory thalamic neurons is widely unknown. To address this knowledge gap and develop a comprehensive model of this circuitry, we will perform whole cell recordings and immunohistochemistry/in situ hybridization on neurons in the thalamic reticular nucleus (Aim 1), cerebellar nuclei, and amygdala (Aim 2) that will identify the function of these pathways at a cellular level. Using an optogenetic approach, we will assess the neurotransmitter released by each projection (Aim 1) and the functional and molecular identity of neurons forming this projection in cerebellar nuclei and amygdala (Aim 2). These data will provide a foundation for identifying the functional impact of cerebellar and/or amygdala projections to the thalamic reticular nucleus regarding dynamics of this network, influence auditory processing in the thalamus, and involvement of these projections in stimulus selection and attention.

项目总结/摘要 听觉信息的精确编码和过滤依赖于听觉丘脑皮层回路， 耳鸣和自闭症谱系障碍（ASD）是由耳鸣和自闭症谱系障碍引起的。在这个回路中，丘脑 网状核影响听觉丘脑皮层神经元的编码和活动，以确定 注意力和刺激选择，但对这个回路的理解是不完整的。很明显，丘脑和皮层 传入神经调节丘脑网状核，但也涉及其他丘脑外皮质脑区 在塑造TRN的感官过滤特性方面。我们假设整合多功能的大脑区域 形成内部预测或确定情绪状态的模态感觉信息对于“调整” TRN神经元通过调节TRN活动、听觉编码和感觉选择的过滤特性 行为。初步数据表明小脑输出核（感觉运动预测）和杏仁核（情感） 直接投射到丘脑网状核-一个抑制感觉丘脑神经元的大脑区域， 调节刺激编码、选择和注意力。小脑和丘脑之间的直接联系 网状核可能是多通道感觉信息传递的重要通道， 关于时间和空间上的周围事件的预测（例如多个声刺激源的变化， 背景噪声等）。同样，杏仁核向丘脑网状核的直接投射可能 提供调节对特定刺激的选择和注意力的情感背景（例如， 紧张的环境）。虽然这些连接的解剖学证据是明确的，但小脑和 杏仁核向丘脑网状核的投射，细胞类型特异性回路，以及随后对 听觉丘脑神经元是广泛未知的。为了解决这一知识差距， 为了建立这种电路的模型，我们将对这些细胞进行全细胞记录和免疫组织化学/原位杂交。 丘脑网状核（Aim 1）、小脑核和杏仁核（Aim 2）中的神经元将识别 这些途径在细胞水平上的功能。使用光遗传学方法，我们将评估神经递质 由每个投射释放（Aim 1）和形成该投射的神经元的功能和分子身份 在小脑核和杏仁核中的分布（Aim 2）。这些数据将为确定功能性 小脑和/或杏仁核投射到丘脑网状核的影响， 网络，影响丘脑中的听觉处理，以及这些投射在刺激中的参与 选择和注意。