Modulatory Circuits in the Auditory System

听觉系统中的调制电路

• 批准号: 9756365
• 负责人: Brett R Schofield
• 金额: $ 52.23万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756365
• 关键词: Acetylcholine; Acoustics; Aging; Area; Arousal; Attention; Auditory; Auditory system; Behavior; Brain; Brain Stem; Cell Nucleus; Cells; Cochlea; Cochlear Implants; Cochlear nucleus; Complex; Conscious; Data; Development; Disease; Ear; Electron Microscopy; Environment; Frequencies; Future; Genetic Engineering; Goals; Hearing; Immunochemistry; Inferior Colliculus; Interneurons; Knowledge; Label; Learning; Medial; Medial geniculate body; Methods; Morphology; Nervous system structure; Neuraxis; Neurons; Neurotransmitters; Octopus; Output; Pathway interactions; Pattern; Perception; Phenotype; Physiological; Physiology; Play; Presbycusis; Process; Rattus; Research; Role; Schizophrenia; Sound Localization; Source; Speech; Speech Discrimination; Speech Sound; Stimulus; Synapses; System; Techniques; Tegmentum Mesencephali; Transgenic Animals; Transgenic Organisms; Viral Vector; anatomical tracing; auditory feedback; auditory nuclei; auditory pathway; auditory reflex; autism spectrum disorder; base; cell type; cholinergic; cholinergic synapse; coping; design; experimental study; hearing impairment; information processing; light microscopy; magnocellular; nerve supply; neuronal cell body; neuronal excitability; normal hearing; optogenetics; prevent; public health relevance; response; selective attention; sensory gating; sensory input; stellate cell

 DESCRIPTION (provided by applicant): 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 bran adapt during normal development, during aging and in response to damage of the ear or central nervous system. The long term goal of this research is to understand how cholinergic inputs to brainstem auditory circuits contribute to these tasks. Recent studies have identified 4 different cholinergic systems that innervate the brainstem auditory pathways. These cholinergic systems have different functions such as arousal, setting neuronal sensitivity, or controlling the flow of auditory information (e.g., to determine whether an acoustic stimulus is consciously perceived). A major obstacle to understand cholinergic functions in the brainstem has been lack of information about which cholinergic sources contact which auditory pathways. The objective of this proposal is to identify brainstem auditory circuits that are major targets of specific brainstm cholinergic projection systems. The experiments will use recently developed viral vectors and genetically-engineered ("transgenic") rats to label cholinergic circuits from identified sources. These techniques will be combined with multi-labeling anatomical tracers and immunochemistry to identify the components and synaptic organization of specific auditory circuits targeted by the cholinergic systems. The Aims focus on two brainstem areas that show high levels of cholinergic innervation: the ventral cochlear nucleus (VCN) and the inferior colliculus (IC). Together, these 2 areas process nearly all auditory information and thus contribute to all aspects of auditory function. Aim 1 will focus on the VCN, a region that receives direct input from the ear and that gives rise to multiple pathways to higher centers. The experiments will identify cholinergic inputs to specific ascending pathways. Aims 2 and 3 will focus on the IC, the largest brainstem auditory center and a major hub for integration of auditory information. Aim 2 will identify specific cell types in the IC that are targeted by cholinergic inputs. Aim 3 will idetify the circuits within the IC that are likely to be modulated by the cholinergic inputs and that could control how auditory information is processed within this integrative center. Overall, results from the three Aims will move the field forward by providing essential information for designing and interpreting future experiments with optogenetics, physiology and behavior to better understand cholinergic roles in normal hearing, during development, learning and aging and after damage to the cochlea or central auditory system.

 描述（由申请人提供）：乙酰胆碱是一种神经递质，在听力的许多方面发挥着作用，包括选择性注意、学习、频率选择性、声音定位和语音辨别，它还在帮助麸皮适应方面发挥着关键作用。这项研究的长期目标是了解脑干听觉回路的胆碱能输入如何促进这些任务。已经确定了支配脑干听觉通路的 4 种不同的胆碱能系统，这些胆碱能系统具有不同的功能，例如唤醒、设置神经敏感性或控制听觉信息流（例如，确定是否有意识地感知声音刺激）。理解脑干胆碱能功能的一个障碍是缺乏关于哪些胆碱能来源接触哪些听觉通路的信息。该提案的目的是识别脑干听觉通路。这些实验将使用最近开发的病毒载体和基因工程（“转基因”）大鼠来标记已确定来源的胆碱能回路。免疫化学来识别胆碱能系统所针对的特定听觉回路的成分和突触组织，目标集中在两个表现出高水平的脑干区域。胆碱能神经支配：腹侧耳蜗核 (VCN) 和下丘 (IC)，这两个区域一起处理几乎所有听觉信息，因此有助于听觉功能的各个方面。目标 1 将重点关注 VCN（接收信息的区域）。来自耳朵的直接输入，产生通往高级中心的多种途径。实验将确定特定上升途径的胆碱能输入，目标 2 和 3 将重点关注最大的 IC。目标 2 将识别 IC 中胆碱能输入所针对的特定细胞类型，目标 3 将识别 IC 内可能受胆碱能输入和调节的电路。那可以 控制听觉信息在这个综合中心内的处理方式。 这三个目标将为设计和解释未来的光遗传学、生理学和行为实验提供重要信息，从而推动该领域向前发展，以更好地了解胆碱能在正常听力、发育、学习和衰老过程中以及耳蜗或中枢听觉系统损伤后的作用。