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  • 學位論文

自主性感光視神經細胞藉由旁支軸突調控視網膜多巴胺分泌而影響光適應現象

M1 intrinsically photosensitive Retinal Ganglion Cells regulate light adaptation through dopamine amacrine cells by intra-retinal axon collateral

指導教授 : 陳示國

摘要


環境照明度是一個重要的環境信息使我們保持正常的生理功能,但是它對我們視覺的貢獻卻仍在爭論之中。視覺系統曾被認為僅藉由光的對比度變化來完成功能,然而因為近期內生感光視神經的研究,環境亮度的效果被認為會參與其中。內生感光視神經細胞是第三類型的視網膜感光細胞,這些細胞表現感光視黑蛋白,並且將信號傳輸到大腦調控日夜週期,瞳孔反射和睡眠調節。過去的研究根據其形態和細胞體大小將內生感光視神經細胞分成至少五種類型,研究也顯示M1類別內生感光視神經細胞旁支軸突會回到視網膜內叢狀層。此外,我們的免疫染色圖也明確指出自主性感光視神經的旁支軸突可能會與多巴胺中介神經細胞形成突觸。由於多巴胺是在視網膜上影響光適應功能的重要物質,我們認為M1內生感光視神經的旁支軸突也可能通過與多巴胺中介神經細胞的連接而涉及視覺功能運作。我們的研究顯示,M1 自主性感光視神經細胞除了可以檢測背景光度水平並把訊息傳給視交叉上核來調控生理時鐘週期之外,同時也能將訊號傳回內叢狀層的多巴胺中介神經細胞來調節光適應現象,且可能還參與其他複雜的視覺功能運作。

關鍵字

神經 視網膜 光適應

並列摘要


Ambient luminance is a vital environmental information for us to maintain our normal physiological function, but its contribution to our visual system is still poorly understood. It has been shown that our visual system primary detect contrast, while the background luminance plays little to no role for pattern forming functions. However, recent evidence has suggested that environment luminance may be involved in vision through intrinsic photosensitive retina ganglion cell (ipRGC), which is the third type of photoreceptor in mouse retina. ipRGCs express melanopsin for light sensing and transmit their signal directly to the brain for circadian photo-entrainment, pupillary light reflex and sleep regulation. Previous studies showed that ipRGCs can be divided into at least five types according to their dendritic morphology and cell body size. Furthermore, recent study showed that M1 type ipRGCs have intra retinal axons collateral innervating retrogradely to the inner plexiform layer (IPL), which could form a putative synapse with dopamine amacrine cells (DACs). Since dopamine is important for the light adaptation, we hypothesize that the M1 ipRGCs may also be involved in visual function through the connection with DACs. Using genetic mouse model and electroretinogram, our study shows that elimination of ipRGCs blocks the light adaptation of cones, while application of D1 or D4 receptor agonist can rescue the light adaptation. Together, our data indicates that ipRGCs could modulate visual function through DACs and probably be involved in higher complicated visual function.

並列關鍵字

ipRGC Retina light adaptation

參考文獻


Reifler, Aaron N., Chervenak, Andrew P., Dolikian, Michael E., Benenati, Brian A., Li, Benjamin Y., Wachter, Rebecca D., Lynch, Andrew M., Demertzis, Zachary D., Meyers, Benjamin S., Abufarha, Fady S., et al. (2015). All Spiking, Sustained ON Displaced Amacrine Cells Receive Gap-Junction Input from Melanopsin Ganglion Cells. Current Biology 25, 2763-2773.
Badea, T.C., and Nathans, J. (2004). Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter. The Journal of comparative neurology 480, 331-351.
Barnard, A.R., Hattar, S., Hankins, M.W., and Lucas, R.J. (2006). Melanopsin regulates visual processing in the mouse retina. Current biology : CB 16, 389-395.
Belenky, M.A., Smeraski, C.A., Provencio, I., Sollars, P.J., and Pickard, G.E. (2003). Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. The Journal of comparative neurology 460, 380-393.
Berson, D.M., Dunn, F.A., and Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science (New York, NY) 295, 1070-1073.

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