Neuronal Plasticity in the Retina

描述（由申请人提供）：本研究项目是一项实验性研究，旨在了解神经网络如何因内在昼夜节律振荡器的影响而改变或适应。在兔视网膜中，初步证据表明昼夜节律时钟（24小时）调节杆状细胞和锥体向神经节细胞和锥体连接的水平细胞（一种接受来自锥体的突触接触的二级细胞）的输入。昼夜节律钟是一种生物振荡器，在没有外部时间提示（如持续黑暗）的情况下，其周期约为24小时，具有持续的节律性。调节神经节细胞和锥体连接水平细胞光反应的昼夜节律因子尚不清楚。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，这些神经调节剂介导视网膜内外视杆和视锥通路上的时钟效应。

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.