Modulatory Circuits in the Auditory System

听觉系统中的调制电路

• 批准号: 10683308
• 负责人: Brett R Schofield
• 金额: $ 59.73万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683308
• 关键词: Acceleration; Acetylcholine; Acoustics; Address; Aging; Anatomy; Area; Arousal; Auditory; Auditory area; Auditory system; Axon; Brain; Brain Stem; Cavia; Cell Nucleus; Cells; Central Nervous System; Cholinergic Receptors; Cochlea; Cochlear Implants; Cochlear nucleus; Complex; Data; Development; Disease; Ear; Environment; Fluorescent in Situ Hybridization; Frequencies; Functional disorder; Future; Goals; Grant; Hearing; Individual; Inferior Colliculus; Knowledge; Label; Learning; Left; Long-Term Effects; Mediating; Methods; Midbrain structure; Muscarinic Acetylcholine Receptor; Nervous System; Neurotransmitters; Nicotinic Receptors; Pathway interactions; Pattern; Perception; Persons; Physiological; Play; Population; Presbycusis; Research; Rewards; Role; Schizophrenia; Sleep Wake Cycle; Sound Localization; Source; Speech; Speech Discrimination; Speech Sound; Synapses; System; Tegmentum Mesencephali; Testing; Thalamic structure; Therapeutic; Tracer; Transgenic Animals; Transgenic Mice; Viral; Viral Vector; auditory feedback; auditory nuclei; auditory pathway; auditory processing; autism spectrum disorder; cell type; cholinergic; coping; design; experimental study; hearing impairment; insight; nerve supply; neuronal excitability; normal hearing; prevent; receptor; response; selective attention; sensory gating

Abstract Acetylcholine is a neurotransmitter that plays a role in many aspects of hearing, including selective attention, learning, frequency selectivity, sound localization, and discrimination of speech sounds. It also plays a critical role in helping the brain adapt during normal development, during aging and in response to damage of the ear or central nervous system. Top-down modulation, in which higher brain centers modify early acoustic processing, contributes to many of these functions, often through interactions with cholinergic pathways. A long-term goal of this research is to understand how cholinergic inputs modulate brainstem auditory processing and how projections from auditory cortex contribute to these functions. The present proposal will address four main gaps in our knowledge that limit our understanding of cholinergic function in the auditory brainstem. The first gap in our knowledge is lack of information on sources of cholinergic input to most brainstem auditory nuclei. Aim 1 will identify these sources by using recently developed viral vectors in newly created transgenic mice. A second gap concerns divergent projections from individual cholinergic cells. Modulatory cells in other brain areas typically have branching axons to allow widespread modulation. Aim 2 will use multi-label tracing in transgenic mice to identify divergent circuits that could support concurrent modulation of large expanses of the auditory brainstem. A third gap is a nearly total lack of information on cholinergic receptor types associated with specific brainstem circuits. Numerous receptor types occur in the subcortical auditory system, suggesting a variety of short- and long-term effects. Aim 3 will combine anatomical tract tracing with fluorescent in situ hybridization (FISH) to identify specific cholinergic receptor components associated with particular ascending and descending auditory circuits. The fourth gap in our knowledge concerns the identity of brainstem cholinergic circuits that are directly contacted by projections from the auditory cortex. Aim 4 will use conventional tracers as well as trans-synaptic intersectional viral methods in transgenic animals to test the hypothesis that cortical projections contact cholinergic cells that innervate many subcortical auditory nuclei. These results will identify the cholinergic circuits that are responsible for cortically-driven release of acetylcholine. Overall, the results from the four Aims will provide fundamental information about brainstem cholinergic circuits, their targets within the auditory pathway, and the extent to which they may be activated by projections from higher brain centers. This information is essential for the design and interpretation of future experiments to understand cholinergic and top-down modulation and for insight into therapeutic approaches to prevent or treat deficits associated with dysfunction of these systems.

摘要 乙酰胆碱是一种神经递质，在听力的许多方面都起着作用，包括选择性注意， 学习、频率选择性、声音定位和语音辨别。它也起到了关键的 在帮助大脑适应正常发育过程中的作用，在老化和对耳朵损伤的反应 或中枢神经系统。自上而下的调制，其中更高的大脑中心修改早期声学 加工，有助于许多这些功能，往往通过与胆碱能途径的相互作用。一 本研究的长期目标是了解胆碱能输入如何调节脑干听觉加工 以及来自听觉皮层的投射如何促成这些功能。本提案将针对四个 我们知识的主要空白限制了我们对听觉脑干胆碱能功能的理解。的 我们知识的第一个缺口是缺乏关于大多数脑干听觉系统胆碱能输入来源的信息。 原子核。目的1将通过使用最近开发的病毒载体在新创建的转基因中鉴定这些来源。 小鼠第二个缺口涉及来自单个胆碱能细胞的不同投射。其他调节细胞 大脑区域通常具有分支轴突以允许广泛的调制。Aim 2将在 转基因小鼠，以确定不同的电路，可以支持同时调制的大规模的 听觉脑干第三个缺口是几乎完全缺乏与胆碱能受体类型相关的信息。 特定的脑干回路许多受体类型出现在皮层下听觉系统，表明 各种短期和长期的影响。目的3将联合收割机解剖追踪与荧光原位相结合 用荧光原位杂交技术（FISH）鉴定与特定的上升神经元相关的特异性胆碱能受体成分。 和下行听觉回路我们知识的第四个空白是关于脑干的身份 与听觉皮层的投射直接接触的胆碱能回路。目标4将使用 传统的示踪剂以及跨突触交叉病毒方法在转基因动物中测试 皮质投射与支配许多皮质下听觉核团的胆碱能细胞接触的假说。 这些结果将确定负责皮质驱动释放的胆碱能回路。 乙酰胆碱总体而言，四个目标的结果将提供有关脑干的基本信息 胆碱能回路，它们在听觉通路中的靶点，以及它们可能被激活的程度。 从更高的大脑中心投射。这些信息对于未来的设计和解释至关重要。 实验，以了解胆碱能和自上而下的调制和洞察治疗方法， 预防或治疗与这些系统功能障碍相关的缺陷。