Circuit Mechanisms for Auditory Processing in the Inferior Colliculus

下丘听觉处理的电路机制

• 批准号: 10623242
• 负责人: Michael Thomas Roberts
• 金额: $ 43.7万
• 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/10623242
• 关键词: Anatomy; Auditory; Auditory Prosthesis; Auditory system; Axon; Brain; Brain Stem; Brain region; Cell Nucleus; Code; Complex; Contralateral; 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; Shapes; Slice; Sound Localization; Source; Speech; Stimulus; Synapses; Synaptic Transmission; System; Testing; Time; Training Activity; Vasoactive Intestinal Peptide; Viral; auditory processing; auditory thalamus; 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.

抽象的 下丘（IC）是中央听觉系统的中脑枢纽。虽然IC是关键 言语，发声和其他复杂声音的处理中心，神经元机制 IC中的计算在很大程度上未知。知识差距仍然存在，因为事实证明它很困难 可靠地识别特定的IC神经元类。通过将分子标记与解剖学和 生理措施，我们最近克服了这一障碍，并确定了两个新的IC类 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 是兴奋性的谷氨酸能神经元，而NPY神经元是抑制性的，GABA能神经元。 VIP和 NPY神经元是具有树突状乔木的星状神经元，它们遍布中央的吨位轴 IC（ICC）的核，并且两者都投射到包括听觉丘脑在内的多个大脑区域。因为 他们可以从多种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，但是星状神经元的功能作用以前具有 难以接近。通过识别VIP和NPY神经元，我们首次拥有该工具可以选择性地 靶标并操纵兴奋性和抑制性的ICC星状神经元。总体目标 建议是为VIP和NPY神经元的输入和输出建立功能性接线图以及 确定VIP和NPY神经元如何响应声音的差异。为了实现这一目标，我们将 使用病毒道追踪，光遗传电路映射，脑切片电生理学和光遗传学靶向 体内录音。在AIM 1中，我们将确定对VIP和NPY神经元的听觉输入的上升来源 并确定这些输入在活动列车中如何改变其突触强度。在AIM 2中，我们将确定 VIP和NPY神经元的远程靶标和末端树树形模式，并确定突触 VIP和NPY神经元的传播会影响丘脑听觉的神经元。在AIM 3中，我们将测试 兴奋性VIP神经元和抑制​​性NPY神经元的假设在对音调和噪声的反应上有所不同 以及振幅和频率调制的声音，代表语音和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 ICC星状神经元的类别，一种兴奋性和一种抑制性，整合了上升和下降的听觉 输入，影响远距离突触后目标，并对简单而复杂的声音做出反应。这些结果将会 关于ICC星状神经元如何促进声音处理的基于证据的假设 为调查言语和发声的电路计算提供了一个调查的发射点 在中脑编码。

项目成果

Inhibitory NPY Neurons Provide a Large and Heterotopic Commissural Projection in the Inferior Colliculus.

• DOI: 10.3389/fncir.2022.871924
• 发表时间: 2022
• 期刊: FRONTIERS IN NEURAL CIRCUITS
• 影响因子: 3.5
• 作者: Anair, Justin D.;Silveira, Marina A.;Mirjalili, Pooyan;Beebe, Nichole L.;Schofield, Brett R.;Roberts, Michael T.
• 通讯作者: Roberts, Michael T.

Neurotransmitter phenotype and axonal projection patterns of VIP-expressing neurons in the inferior colliculus.

• DOI: 10.1016/j.jchemneu.2022.102189
• 发表时间: 2022-12
• 期刊: JOURNAL OF CHEMICAL NEUROANATOMY
• 影响因子: 2.8
• 作者: Beebe, Nichole L.;Silveira, Marina A.;Goyer, David;Noftz, William A.;Roberts, Michael T.;Schofield, Brett R.
• 通讯作者: Schofield, Brett R.

Neuropeptide Y signaling regulates recurrent excitation in the auditory midbrain.

神经肽 Y 信号传导调节听觉中脑的反复兴奋。

• DOI: 10.1101/2023.05.16.540954
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Silveira,MarinaA;Drotos,AudreyC;Pirrone,TrinityM;Versalle,TrevorS;Bock,Amanda;Roberts,MichaelT
• 通讯作者: Roberts,MichaelT

Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus.

胆碱能布顿沿下丘 VIP 神经元的树突和胞体分布。

• DOI: 10.1007/s10162-022-00885-9
• 发表时间: 2023
• 期刊: Journal of the Association for Research in Otolaryngology : JARO
• 作者: Kwapiszewski,JuliaT;Rivera-Perez,LuisM;Roberts,MichaelT
• 通讯作者: Roberts,MichaelT

Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.

谱系追踪揭示了下丘中 NPY 神经元数量的增加。

• DOI: 10.1101/2024.03.27.587042
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Silveira,MarinaA;Herrera,YoaniN;Beebe,NicholeL;Schofield,BrettR;Roberts,MichaelT
• 通讯作者: Roberts,MichaelT