Cholinergic Circuits in the Ventral Cochlear Nucleus

耳蜗腹核中的胆碱能回路

• 批准号: 8829476
• 负责人: Nichole L Beebe
• 金额: $ 2.69万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8829476
• 关键词: Acetylcholine; Affect; Area; Arousal; Attention; Auditory; Auditory system; Brain; Cell Nucleus; Cells; Choline O-Acetyltransferase; Cholinergic Agonists; Cochlea; Cochlear nucleus; Complex; Contralateral; D Cells; Data; Detection; Development; Disease; Electron Microscopy; Experimental Designs; Grant; Hearing; Hearing problem; Immunochemistry; Immunohistochemistry; Inferior Colliculus; Injection of therapeutic agent; Label; Link; Medial; Methods; Midbrain structure; Mus; Neuroanatomy; Neuromodulator; Neurons; Neurotransmitters; Noise; Octopus; One-Step dentin bonding system; Output; Pathway interactions; Physiological; Play; Process; Relative (related person); Research Methodology; Role; Sensory; Sensory Process; Signal Transduction; Site; Source; Synapses; Synaptic plasticity; System; T-Lymphocyte; Techniques; Technology; Testing; Tinnitus; Tracer; Training; Uncertainty; Viral; Writing; acetylcholine transporter; base; career development; cell type; cholinergic; cholinergic synapse; dorsal cochlear nucleus; hearing impairment; insight; light microscopy; magnocellular; neural circuit; neuronal cell body; public health relevance; research study; sensory gating; sound; stellate cell; tool

DESCRIPTION (provided by applicant): All auditory information enters the brain at the cochlear nucleus, making this nucleus one of the first opportunities for modulation of incoming auditory information. Acetylcholine is an important neuromodulator present in the cochlear nucleus, and has been linked to processes such as gain adjustment, encoding of spectral peaks, selective auditory attention, and arousal. The role of cholinergic modulation in the cochlear nucleus is likely closely linked to the source providing the acetylcholine. Previously, it was believed that all acetylcholine in the ventral cochlear nucleus originated in the superior olivary complex; however a recent study found a cholinergic projection to the cochlear nucleus from areas in the midbrain associated with attention and arousal. Currently, little is known about this projection and how it might interact with other sources of cholinergic projections to the cochlear nucleus. This proposal focuses on the ventral division of the cochlear nucleus, and seeks to understand the circuitry of its cholinergic inputs. The first aim will identify the source of acetylcholine in the ventral cochlear nucleus. The second aim will associate cholinergic sources with cell types in the ventral cochlear nucleus. The third aim will identify connections between cholinergic inputs and specific output pathways of the ventral cochlear nucleus. These experiments will be accomplished using fluorescent and viral tracers to examine neurons projecting to and from the ventral cochlear nucleus. Immunochemistry will be used to determine whether tracer-labeled cells and terminals are cholinergic. Light microscopy will be used to find probable points of contact between cholinergic terminals and cells in the ventral cochlear nucleus, and electron microscopy will be used to confirm synaptic contacts. All experiments will be conducted in mice, as they are widely used in auditory research, and the methods proposed have been validated in this species. The results will provide important information about the sources of acetylcholine to the ventral cochlear nucleus and, by definitively linking cholinergic inputs to specific output pathways, will move one step toward understanding the roles of these inputs. These results have important implications for understanding normal auditory function, and for understanding pathological conditions. Acetylcholine in the cochlear nucleus has been demonstrated to play a role in hearing loss and tinnitus, making these results valuable to the study of both of these disorders. In addition to providing important scientific information, this proposal will allow training of the applicant in multiple anatomical techniques, experimental design, and light and electron microscopy as well as additional aspects of scientific career development such as grant writing and management.

描述（由申请人提供）：所有听觉信息都进入人工耳蜗的大脑，使该核成为调节传入听觉信息的第一个机会之一。乙酰胆碱是人工耳蜗中存在的重要神经调节剂，并且已与工艺相关，例如增益调节，光谱峰的编码，选择性听觉注意力和唤醒。胆碱能调节在人工耳蜗核中的作用可能与提供乙酰胆碱的来源密切相关。以前，它 人们认为腹侧耳蜗核中的所有乙酰胆碱都起源于上橄榄络合物。然而，最近的一项研究发现，与注意力和唤醒相关的中脑区域对耳蜗核的胆碱能投射。当前，对该投影及其如何与耳蜗核的其他胆碱能预测来源相互作用知之甚少。该提议着重于人工耳蜗的腹侧分裂，并试图了解其胆碱能输入的电路。第一个目的将鉴定腹侧耳蜗核中乙酰胆碱的来源。第二个目标将使胆碱能源与腹侧耳蜗核中的细胞类型相关联。第三个目标将确定胆碱能输入与腹侧耳蜗核的特定输出途径之间的连接。这些实验将使用荧光和病毒示踪剂进行检查，以检查与腹侧耳蜗核突出的神经元。免疫化学将用于确定示踪剂标记的细胞和末端是否是胆碱能。光学显微镜将用于查找腹侧耳蜗核中胆碱能末端和细胞之间的接触点，并将使用电子显微镜来确认突触接触。所有实验将在小鼠中进行，因为它们在听觉研究中广泛使用，并且提出的方法已在该物种中得到验证。结果将提供有关乙酰胆碱来源到腹侧耳蜗核的重要信息，并通过将胆碱能输入与特定的输出途径联系起来，将朝着理解这些输入的作用迈出一步。这些结果对理解正常听觉功能和理解病理状况具有重要意义。已证明人耳蜗核中的乙酰胆碱可以在听力损失和耳鸣中发挥作用，使这些结果对这两种疾病的研究都很有价值。除了提供重要的科学信息外，该建议还将允许对申请人进行多种解剖技术，实验设计以及光和电子显微镜以及科学职业发展（例如赠款写作和管理）的其他方面进行培训。