Molecular regulation of auditory innervation

听觉神经支配的分子调节

• 批准号: 7365190
• 负责人: YAEL RAZ
• 金额: $ 19.28万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7365190
• 关键词: Apical; Area; Auditory; Auditory Brainstem Responses; Axon; Clinical Treatment; Cochlea; Cochlear Implants; Cochlear implant procedure; Commit; Coupled; Cues; Dendrites; Development; Devices; Discrimination; Electrodes; Elements; Fostering; Frequencies; Gene Deletion; Gene Expression; Genes; Goals; Growth; Hair Cells; Hearing; In Vitro; Individual; Institution; Knowledge; Labyrinth; Ligands; Mentors; Messenger RNA; Molecular; Mus; Neuraxis; Neurites; Neuritis; Neurons; Pathway interactions; Pattern; Peripheral; Play; Process; Proteins; Regulation; Research; Research Personnel; Resources; Role; Scala Tympani; Sensorineural Hearing Loss; Signal Pathway; System; Testing; Therapeutic Intervention; Time; Visual; axonal guidance; career; ganglion cell; hair cell regeneration; hearing impairment; implantable device; improved; in vivo; member; migration; nerve supply; novel; novel therapeutics; receptor; relating to nervous system; somatosensory; spiral ganglion; stem cell therapy

DESCRIPTION (provided by applicant): Precise targeting of afferent auditory projections is critical for hearing yet the molecular cues which guide axonal path finding in the developing cochlea are not well understood. In other developing systems, the slit/robo signaling pathway provides critical guidance to both axonal and dendritic processes. Members of this pathway are expressed in the mammalian inner ear during the period of neurite outgrowth but their function in the cochlea is not known. The objective of the proposed research is to determine whether slit and robo serve as guidance cues for auditory neuritis. The specific aims are: 1.) To determine the temporo-spatial expression pattern of slit and robo in the developing cochlea; 2.) To determine the effect of exogenous slit on neurite outgrowth in spiral ganglion neurons 3.) To determine whether deletion of slit genes results in misguidance of auditory axons. The identification of molecules involved in axonal path finding in the developing cochlea may impact the clinical treatment of sensorineural haring loss. These molecules could potentially be coupled to a cochlear implant to promote contact between afferent dendrites and the device. Additionally, as progress is made in the area of hair cell regeneration, improved understanding the axonal guidance factors will prove vital for building connections between these new elements and the central nervous system. The candidate is a neurotologist with a research background in auditory development. Her career goal is to integrate advances in inner ear development into novel therapeutic interventions for hearing loss. Her institution is committed to this goal and has provided the necessary space, protected time, and resources. She has put together a team of mentors who can not only provide extensive scientific guidance, but also foster her development as an independent investigator.

描述（由申请人提供）：准确的靶向传入听觉预测对于听到听力至关重要，但指导发育中心的轴突路径发现的分子提示尚不清楚。 在其他开发系统中，狭缝/机器人信号通路为轴突和树突过程提供了关键的指导。 在神经突生长期间，该途径的成员在哺乳动物的内耳中表达，但尚不清楚它们在耳蜗中的功能。 拟议的研究的目的是确定缝隙和机器人是否充当听觉神经炎的指导线索。 具体目的是：1。）确定发育中的耳蜗中狭缝和机器人的颞空间表达模式； 2.）确定螺旋神经节神经元中外源性裂缝对神经突生长的影响3.）确定缝隙基因的缺失是否导致听觉轴突的错误指导。 在发育中的耳蜗中涉及轴突路径发现的分子的鉴定可能会影响感觉神经性刺激损失的临床治疗。 这些分子可能会偶联与人工耳蜗，以促进传入的树突与设备之间的接触。 此外，随着在毛细胞再生领域取得的进展，改善的理解轴突引导因素将被证明对于建立这些新元素与中枢神经系统之间的联系至关重要。 候选人是具有听觉发展研究背景的神经科学家。 她的职业目标是将内耳发展的进步纳入新颖的听力损失治疗干预措施。 她的机构致力于这一目标，并提供了必要的空间，受保护的时间和资源。 她组建了一个导师团队，他们不仅可以提供广泛的科学指导，而且还可以促进她作为独立调查员的发展。