Cholinergic inputs to excitatory and inhibitory midbrain auditory circuits

兴奋性和抑制性中脑听觉回路的胆碱能输入

• 批准号: 8661156
• 负责人: Jeffrey Garrett Mellott
• 金额: $ 5.89万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661156
• 关键词: Acetylcholine; Address; Affect; Aging; Amygdaloid structure; Area; Arousal; Auditory; Auditory area; Auditory system; Autistic Disorder; Axon; Behavioral; Brain; Brain Stem; Cavia; Cells; Cochlear Implants; Data; Detection; Disease; Dorsal; Ear; Electron Microscope; Electron Microscopy; Elements; Employee Strikes; Environment; Fluorescence Microscopy; Functional disorder; Future; Geniculate body structure; Goals; Immunochemistry; Implant; In Vitro; Inferior Colliculus; Injury; Label; Lead; Learning; Light Microscope; Location; Medial; Medial geniculate body; Mediating; Methods; Midbrain structure; Modeling; Neurons; Neurotransmitters; Pathway interactions; Perception; Persons; Physiological; Play; Presbycusis; Process; Research; Role; Schizophrenia; Sensory; Source; Speech; Stimulus; Synapses; System; Techniques; Testing; Tinnitus; Tissues; Tracer; Training; auditory nuclei; auditory pathway; cholinergic; conditioned fear; design; gamma-Aminobutyric Acid; hearing impairment; improved; in vivo; light microscopy; neural circuit; receptor; research study; selective attention; somatosensory

DESCRIPTION (provided by applicant): The auditory system comprises ascending pathways that transmit information from the ear to higher levels for perception, and descending pathways that can modify how that information is processed at each auditory nucleus. Descending projections from auditory cortex to the inferior colliculus of the midbrain play a role in a wide range of auditory functions, including selective attention, plasticity and learning, and understanding speech in noisy environments. Recent progress indicates that cholinergic cells (neurons that use acetylcholine as a neurotransmitter) play an important role in many of these functions. Many of the cholinergic effects are mediated through interactions with GABAergic cells (neurons that use GABA as a neurotransmitter) in the inferior colliculus, but further understanding has been hindered by questions regarding the underlying neural circuitry. The present proposal focuses on possible connections between the cholinergic and descending systems to a recently discovered GABAergic pathway from cells of the inferior colliculus to the medial subdivision of the medial geniculate body. One aim is to identify the locations of these cells across the functional subdivisions of the inferior colliculus cells. The second and third aim determine whether these cells receive cholinergic or auditory cortical inputs. The study will be conducted in guinea pigs, a well-researched model for many aspects of auditory function. The experiments will use multilabeling anatomical techniques, including fluorescent neuronal tracers for labeling specific circuit elements and immunochemical techniques for identifying the neurotransmitters associated with those elements. Coordinated studies with both light and electron microscopes will allow for the direct identification of synapses, a necessary step for identifying neuronal circuits. The results will provide an important step in characterizing excitatory and inhibitory midbrain circuits and their relationships to ascending and descending auditory pathways as well as their relationships to the cholinergic system. This may have important implications for normal function as well as dysfunction (such as presbycusis or tinnitus) associated with aging or injury and for the evolving design and use of cochlear implants and brainstem implants. From a training perspective, the proposed experiments cover a broad range of sensitive anatomical techniques, including a variety of multi-labeling methods and strategies for the effective combination of light and electron microscopy. This anatomical training is designed to expand and diversify the applicant's prior limited training in neuroanatomical techniques. The ability to combine and analyze multiple anatomical approaches will greatly expand the range of research questions that he will be able to address in the future.

描述（由申请人提供）：听觉系统包括将信息从耳朵传输到更高层次以进行感知的上行路径，以及可以修改每个听觉核处理信息的方式的下行路径。从听觉皮层到中脑下丘的下降投射在广泛的听觉功能中发挥着作用，包括选择性注意、可塑性和学习，以及在嘈杂环境中理解言语。最近的进展表明胆碱能细胞（使用乙酰胆碱作为神经递质的神经元）在许多这些功能中发挥着重要作用。许多胆碱能效应是通过与下丘中的 GABA 能细胞（使用 GABA 作为神经递质的神经元）相互作用介导的，但有关潜在神经回路的问题阻碍了进一步的理解。目前的提议重点关注胆碱能和下行系统与最近发现的从下丘细胞到内侧膝状体内侧细分的 GABA 能通路之间可能的联系。目的之一是确定这些细胞在下丘细胞功能分区中的位置。第二个和第三个目标确定这些细胞是否接收胆碱能或听觉皮层输入。这项研究将在豚鼠身上进行，豚鼠是听觉功能许多方面经过深入研究的模型。这些实验将使用多标记解剖技术，包括用于标记特定电路元件的荧光神经元示踪剂和用于识别与这些元件相关的神经递质的免疫化学技术。光学显微镜和电子显微镜的协调研究将允许直接识别突触，这是识别神经元回路的必要步骤。这些结果将为表征兴奋性和抑制性中脑回路及其与上升和下降听觉通路的关系以及它们与胆碱能系统的关系提供重要的一步。这可能对正常功能以及与衰老或损伤相关的功能障碍（例如老年性耳聋或耳鸣）以及耳蜗植入物和脑干植入物的不断发展的设计和使用产生重要影响。 从训练的角度来看，所提出的实验涵盖了广泛的敏感解剖技术，包括各种多标记方法和光学和电子显微镜有效结合的策略。这种解剖学培训旨在扩展申请人之前有限的神经解剖技术培训并使其多样化。结合和分析多种解剖方法的能力将极大地扩大他未来能够解决的研究问题的范围。