Electrical activity and spiral ganglion neuron survival

电活动和螺旋神经节神经元存活

• 批准号: 7060853
• 负责人: Damon A Fairfield
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060853
• 关键词: acoustic nerve; biological signal transduction; cAMP response element binding protein; calcium channel; calcium channel blockers; calcium flux; calmodulin dependent protein kinase; cochlear implants; ear /hearing prosthesis; evoked potentials; ganglion cell; laboratory rat; medical implant science; neural conduction; neural degeneration; neural plasticity; neural transmission; oscillography; postdoctoral investigator; protein kinase A; voltage gated channel

DESCRIPTION (provided by applicant): To date, nearly all in vitro studies examining the role of membrane depolarization on spiral ganglion neuron (SGN) survival have used chronic depolarization as a model. These studies demonstrated the requirement of cytosolic Ca2+ for the neurotrophic effects of depolarization; however, chronic depolarization is an imperfect model of physiological neural activity, which occurs as patterns of brief bursts of depolarization. There is accumulating evidence that different patterns of Ca2+ oscillations result in different patterns of intracellular signaling. Moreover, under conditions of chronic depolarization only a single voltage-gated Ca2+ channel (the L-type channel) is open, while others are inactivated. This suggests that the signaling pathways activated by chronic depolarization and patterned activity may differ. In the present study I test this by examining the effect of patterned activity on SGN survival, determine how these patterns modulate cytosolic Ca2+, and identify the signaling pathways that promote SGN survival. These studies will identify pathways involved with activity-dependent SGN survival. The result will allow the correlation of electrical stimulation patterns used in cochlear implants with their long-term effects on SGN survival in vivo.

描述（由申请人提供）：迄今为止，几乎所有研究膜去极化对螺旋神经节神经元（SGN）生存的作用的研究都将慢性去极化作为模型。这些研究证明了胞质Ca2+对去极化的神经营养作用的要求。然而，慢性去极化是生理神经活动的不完善模型，它是短暂去极化爆发的模式。有积极的证据表明，CA2+振荡的不同模式会导致不同的细胞内信号传导。此外，在慢性去极化的条件下，只有一个电压门控的Ca2+通道（L型通道）开放，而其他电源则被灭活。这表明由慢性去极化和图案化活性激活的信号通路可能有所不同。在本研究中，我通过检查图案活性对SGN存活的影响，确定这些模式如何调节胞质Ca2+并确定促进SGN存活的信号传导途径。这些研究将确定与活动依赖性SGN存活有关的途径。结果将允许在人工耳蜗中使用的电刺激模式与对体内SGN存活的长期影响。