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: 10452595
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452595
• 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.

项目概要/摘要 听觉信息的准确编码和过滤取决于听觉丘脑皮质回路， 其功能障碍与耳鸣和自闭症谱系障碍（ASD）有关。在这个回路中，丘脑 网状核影响听觉丘脑皮质神经元编码和活动以确定参数 注意力和刺激选择，但对这个电路的理解是不完整的。显然，丘脑和皮质 传入神经调节丘脑网状核，但其他丘脑皮质外脑区也参与其中 塑造 TRN 的感官过滤特性。我们假设整合多种功能的大脑区域 形成内部预测或确定情绪状态的模态感觉信息对于“调整”情绪很重要 通过调节 TRN 活动、听觉编码和感觉选择来过滤 TRN 神经元的特性 行为。初步数据表明小脑输出核（感觉运动预测）和杏仁核（情绪） 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 网状核可能是传递多模态感觉信息和相关信息的重要渠道 对周围时间和空间事件的预测（例如多个声刺激源的变化， 背景噪音等）。同样，从杏仁核到丘脑网状核的直接投射可能 提供情绪背景来调节对特定刺激的选择和注意（例如，增强对特定刺激的感知） 压力环境）。虽然这些联系的解剖学证据是明确的，但小脑和大脑的功能 杏仁核投射到丘脑网状核、细胞类型特异性电路以及随后的影响 听觉丘脑神经元尚不为人所知。为了解决这一知识差距并制定全面的 该电路的模型，我们将进行全细胞记录和免疫组织化学/原位杂交 丘脑网状核（目标 1）、小脑核和杏仁核（目标 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 每个投射（目标 1）释放的信息以及形成该投射的神经元的功能和分子特性 在小脑核和杏仁核中（目标 2）。这些数据将为识别功能提供基础 小脑和/或杏仁核投射到丘脑网状核的影响关于其动力学 网络，影响丘脑的听觉处理，以及这些投射在刺激中的参与 选择和关注。