Circuit Mechanisms for Auditory Processing in the Inferior Colliculus

下丘听觉处理的电路机制

• 批准号: 10188494
• 负责人: Michael Thomas Roberts
• 金额: $ 43.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-10 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10188494
• 关键词: Anatomy; Auditory; Auditory Prosthesis; Auditory system; Axon; Brain; Brain Stem; Brain region; Cell Nucleus; Code; Complex; Data; Dendrites; Electrophysiology (science); Excitatory Synapse; Exhibits; Family; Frequencies; Glutamates; Hearing; Inferior Colliculus; Inhibitory Synapse; Intervention; Investigation; Knowledge; Label; Maps; Measures; Midbrain structure; Molecular; Morphology; Neurons; Neurophysiology - biologic function; Noise; Outcomes Research; Output; Pattern; Physiological; Physiology; Play; Population; Process; Property; Research; Role; Sampling; Slice; Sound Localization; Source; Speech; Stimulus; Synapses; Synaptic Transmission; Testing; Time; Training Activity; Vasoactive Intestinal Peptide; Viral; auditory processing; auditory thalamus; base; evidence base; excitatory neuron; experimental study; falls; hearing impairment; improved; in vivo; inhibitory neuron; insight; molecular marker; neural circuit; neuropeptide Y; novel; optogenetics; postsynaptic; postsynaptic neurons; receptive field; response; sound; sound frequency; speech in noise; speech recognition; stellate cell; superior colliculus Corpora quadrigemina; tool; vocalization

Abstract The inferior colliculus (IC) is the midbrain hub of the central auditory system. Although the IC is a critical processing center for speech, vocalizations, and other complex sounds, the neuronal mechanisms underlying computations in the IC remain largely unknown. This gap in knowledge persists because it has proven difficult to reliably identify specific classes of IC neurons. By combining molecular markers with anatomical and physiological measures, we recently overcame this obstacle and have identified two novel classes of IC principal neurons: vasoactive intestinal peptide (VIP) neurons and neuropeptide Y (NPY) neurons. VIP neurons are excitatory, glutamatergic neurons, while NPY neurons are inhibitory, GABAergic neurons. Both VIP and NPY neurons are stellate neurons with dendritic arbors that spread across the tonotopic axis of the central nucleus of the IC (ICc), and both project to multiple brain regions, including the auditory thalamus. Because they can sample input from a range of sound frequencies, it has long been hypothesized that ICc stellate neurons play important roles in sound processing, but the functional roles of stellate neurons have previously been inaccessible. By identifying VIP and NPY neurons, we possess the tools for the first time to selectively target and manipulate an excitatory and an inhibitory class of ICc stellate neurons. The overall objective of this proposal is to establish a functional wiring diagram for the inputs and outputs of VIP and NPY neurons and to determine the differences in how VIP and NPY neurons respond to sounds. To pursue this objective, we will use viral tract tracing, optogenetic circuit mapping, brain slice electrophysiology, and optogenetically-targeted in vivo recordings. In Aim 1, we will identify the ascending sources of auditory input to VIP and NPY neurons and determine how these inputs vary their synaptic strength during trains of activity. In Aim 2, we will identify the long-range targets and terminal arborization patterns of VIP and NPY neurons and determine how synaptic transmission from VIP and NPY neurons influences neurons in the auditory thalamus. In Aim 3, we will test the hypothesis that excitatory VIP neurons and inhibitory NPY neurons differ in their responses to tones and noise and to amplitude- and frequency-modulated sounds, stimuli that represent important features of speech and other vocalizations. The expected outcome of this research is that we will determine for the first time how two classes of ICc stellate neurons, one excitatory and one inhibitory, integrate ascending and descending auditory input, influence long-range postsynaptic targets, and respond to simple and complex sounds. These results will generate evidence-based hypotheses about how ICc stellate neurons contribute to sound processing and will provide a launching point for investigations into the circuit computations that underlie speech and vocalization coding in the midbrain.

摘要 下丘（IC）是中枢听觉系统的中脑中枢。虽然IC是一个关键的 语音、发声和其他复杂声音的处理中心， IC中的计算在很大程度上仍然未知。这种知识差距之所以持续存在，是因为 以可靠地识别特定类别的IC神经元。通过将分子标记与解剖学和 通过生理学方法，我们最近克服了这一障碍，并确定了两类新的IC 主要神经元：血管活性肠肽（VIP）神经元和神经肽Y（NPY）神经元。VIP神经元 神经肽Y神经元是兴奋性的谷氨酸能神经元，而神经肽Y神经元是抑制性的GABA能神经元。VIP和 NPY神经元是星状神经元，其树突状乔木分布在中枢神经系统的张力轴上。 IC核（ICc），并且两者都投射到多个大脑区域，包括听觉丘脑。因为 它们可以从一系列声音频率中采样输入，长期以来一直假设ICc星状 神经元在声音处理中起重要作用，但星状神经元的功能作用以前 无法接近。通过识别VIP和NPY神经元，我们第一次拥有了选择性地 靶向并操纵ICc星状神经元兴奋性和抑制性类别。本报告的总体目标 建议是建立VIP和NPY神经元输入和输出的功能接线图， 确定VIP和NPY神经元对声音反应的差异。为达致这个目标，我们会 使用病毒道追踪、光遗传学电路映射、脑切片电生理学和光遗传学靶向 体内记录。在目标1中，我们将识别VIP和NPY神经元的听觉输入的上行来源 并确定这些输入在一连串活动中如何改变它们的突触强度。在目标2中，我们将确定 VIP和NPY神经元的长程靶点和终末分支模式，并确定突触如何在神经元中表达。 来自VIP和NPY神经元的传递影响听觉丘脑中的神经元。在目标3中，我们将测试 假设兴奋性VIP神经元和抑制性NPY神经元对音调和噪声的反应不同 以及调幅和调频声音，代表语音重要特征的刺激， 其他发声这项研究的预期结果是，我们将首次确定两个 一类ICc星状神经元，一个兴奋性和一个抑制性，整合上行和下行听觉 输入，影响远距离突触后靶点，并对简单和复杂的声音作出反应。这些结果将 产生关于ICc星状神经元如何有助于声音处理的基于证据的假设，并将 为研究语言和发声的电路计算提供了一个起点 在中脑编码