Neurochemical Interactions of Co-localized Transmitters in The Inner Ear

这项行动是建议为研究耳朵中的神经递质提供三年的资金。神经系统中的细胞形成功能性连接，称为突触；一种用于在突触间传递信息的生化化合物被称为神经递质。神经递质的合成、释放、摄取和转换在信息加工中起着关键作用；其他化合物对这些步骤的调节从而调节了信息传递。人们对内耳中的神经递质或神经调节剂知之甚少，内耳提供了一个具有多种神经活性物质的模型系统来研究它们之间可能的相互作用。这个项目将量化内耳耳蜗内的神经化学相互作用。耳蜗包含听觉受体细胞，这些细胞在听觉神经纤维上形成突触，将信号传递给大脑；此外，还有一种被称为传出神经的纤维，它将信号从大脑的某些中央区域传递到耳蜗。传出通路显然对传入听觉通路的感觉传递起调节作用。听觉递质释放可能受到影响，或者听神经末梢的分子受体位点可能受到传出末梢释放的神经调节剂的影响。因此，听觉通路中的第一个突触可以被认为是一个“多递质”突触。包含耳蜗和神经的骨壳将被原位用作灌注室，以研究两大类候选神经调节剂：阿片肽和乙酰胆碱的释放、降解和受体相互作用。液相色谱法、放射免疫测定法和放射受体测定法将明确地鉴定和定量耳蜗组织中取样的神经活性物质。为了研究可能的共传递机制，该空间的灌注将用于收集响应刺激的神经活性物质，并在突触受体部位注入已知具有激动剂或拮抗剂作用的特定物质。感觉生理学和知觉项目建议资助这个项目，因为它使用了一种全新的方法来阐明听觉系统中的生化机制，并且所阐明的原理可能适用于大脑其他地方神经递质的其他相互作用。

This action is to recommend funding for three years to study neurotransmitters in the ear. Cells in the nervous system make functional connections called synapses; a biochemical compound used to transmit information across a synapse is called a neurotransmitter. The synthesis, release, uptake and turnover of neurotransmitters play key roles in information processing; the regulation of these steps by other compounds thus modulate the information transfer. Not much is known about the neurotransmitters or neuromodulators in the inner ear, and this organ provides a model system with several neuroactive substances to study their possible interactions. This project will quantify the neurochemical interactions within the cochlea of the inner ear. The cochlea contains the auditory receptor cells which synapse on fibers of the auditory nerve that carry signals to the brain; in addition, there are fibers called efferents that carry signals from certain central brain regions out to the cochlea. The efferent pathway apparently acts to modulate the sensory transmission coming in to the auditory pathway. The auditory transmitter release may be affected, or the molecular receptor sites on the auditory nerve terminals may be affected by neuromodulators released from the efferent terminals. Thus this first synapse in the auditory pathway can be considered a "multitransmitter" synapse. The bony shell containing the cochlea and nerve will be used in situ as a perfusion chamber to study the release, degredation and receptor interactions of two major classes of neuromodulator candidates: the opioid peptides and acetylcholine. Liquid chromatography, radioimmune assays and radioreceptor assays will unambiguously identify and quantify the neuroactive substances sampled from the cochlear tissues. To study mechanisms of possible co- transmission, perfusion of this space will be used to collect neuroactive substances in response to stimulation, and to infuse specific substances that have known agonist or antagonist actions at the synaptic receptor sites. The Program in Sensory Physiology & Perception recommends funding this project because it uses a cleaver, novel preparation to clarify the biochemical mechanisms involved in the auditory system, and the principles elucidated are likely to be applicable to other interactions of neurotransmitters elsewhere in the brain.