Neuronal Plasticity in the Retina

视网膜神经元可塑性

• 批准号: 7127453
• 负责人: STUART C MANGEL
• 金额: $ 36.25万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127453
• 关键词: adenosine; circadian rhythms; cone cell; dark adaptation; dopamine; electrochemistry; electrophysiology; high performance liquid chromatography; horizontal cell; laboratory mouse; laboratory rabbit; light adaptations; melatonin; microelectrodes; neural plasticity; retinal adaptation; retinal bipolar neuron; retinal ganglion; rod cell

DESCRIPTION (provided by applicant): This research project is an experimental study that seeks to understand how neuronal networks change or adapt due to the influence of an intrinsic circadian oscillator. In the rabbit retina, preliminary evidence indicates that a circadian (24-hour) clock regulates rod and cone input to ganglion cells and cone-connected horizontal cells, a type of second order cell that receives synaptic contact from cones. A circadian clock is a type of biological oscillator that has persistent rhythmicity with a period of approximately 24 hours in the absence of external timing cues (e.g. constant darkness). The circadian factors that regulate the light responses of ganglion cells and cone-connected horizontal cells are not known. Preliminary evidence suggests that a clock in the retina regulates the release of endogenous dopamine and adenosine and that these neuromodulators mediate the clock effects on rod and cone pathways in the inner and outer retina. We will use electrophysiological, neurochemical and anatomical techniques to determine whether a circadian clock affects the light responses of outer and inner retinal neurons in the mammalian retina (i.e. horizontal, ganglion and All amacrine cells) and whether and how the clock utilizes dopamine, adenosine, and melatonin to achieve its effects. We will also determine whether there is a clock in the mammalian retina that regulates endogenous dopamine and adenosine release and extracellular pH and whether this clock is in the outer or inner retina. Finally, we will characterize the mechanisms by which the mammalian clock regulates the release of dopamine and adenosine. The light responses and tracer coupling of cone-connected horizontal cells and All amacrine cells, as well as the light responses of ganglion cells will be studied under conditions of constant darkness in the day and night, using in vitro rabbit and mouse retinal preparations. Disruption of circadian clock processes in the retina may mediate photoreceptor cell degeneration. Thus, increased understanding of circadian clock processes and pathways and of transmitter function will aid in the understanding of human retinal processes and dysfunction, as well as provide the basis for drug therapy for retinal disorders. In addition, increased knowledge of the action of dopamine and adenosine in the retina may aid in the understanding and treatment of Parkinson's disease and schizophrenia.

描述（由申请人提供）：该研究项目是一项实验研究，旨在了解神经元网络如何因内在昼夜节律振荡器的影响而变化或适应。在兔子的视网膜中，初步证据表明昼夜节律（24 小时）时钟调节神经节细胞和视锥细胞连接的水平细胞（一种接收来自视锥细胞的突触接触的二阶细胞）的视杆细胞和视锥细胞输入。生物钟是一种生物振荡器，在没有外部计时线索（例如持续黑暗）的情况下，具有持续的节律性，周期约为 24 小时。调节神经节细胞和锥连接水平细胞光反应的昼夜节律因素尚不清楚。初步证据表明，视网膜中的时钟调节内源性多巴胺和腺苷的释放，并且这些神经调节剂介导对内视网膜和外视网膜的视杆细胞和视锥细胞通路的时钟效应。 我们将使用电生理学、神经化学和解剖学技术来确定生物钟是否影响哺乳动物视网膜中的外部和内部视网膜神经元（即水平细胞、神经节细胞和所有无长突细胞）的光反应，以及生物钟是否以及如何利用多巴胺、腺苷和褪黑激素来实现其效果。我们还将确定哺乳动物视网膜中是否存在调节内源性多巴胺和腺苷释放以及细胞外pH值的时钟，以及该时钟是否位于视网膜外层或内层。最后，我们将描述哺乳动物生物钟调节多巴胺和腺苷释放的机制。将使用体外兔和小鼠视网膜制剂，在白天和夜间持续黑暗的条件下研究视锥连接的水平细胞和所有无长突细胞的光响应和示踪剂耦合，以及神经节细胞的光响应。 视网膜生物钟过程的破坏可能会介导感光细胞变性。因此，增加对生物钟过程和途径以及递质功能的了解将有助于了解人类视网膜过程和功能障碍，并为视网膜疾病的药物治疗提供基础。此外，增加对视网膜中多巴胺和腺苷作用的了解可能有助于理解和治疗帕金森病和精神分裂症。