2014-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/691265摘要：哺乳動物視網膜的光線感知傳統上被認為是單向的路徑：視桿與視錐細胞偵測光子，訊號經雙極細胞（bipolar cell）傳送至視神經細胞（retinal ganglion cell, RGC），並且由水平細胞（horizontal cell）與無軸突細胞（amacrine cell）進行其間的運算；視神經細胞為視網膜內唯一將訊息由軸突輸出至腦區的神經細胞，一般認為視神經細胞不會藉由軸突分枝（axon collateral）將訊息帶回到視網膜。研究指出有一小群視神經細胞，即能夠表現感光色素「視黑質（melanopsin）」的感光視神經細胞（intrinsically photosensitive retinal ganglion cell, ipRGC）。藉由基因表現性狀及外形特徵，ipRGC可被區分為不同的族群並且控制不同的生理功能 (Nature 476, 2011)，並且不同族群也可以在視網膜自行形成均勻的分布 (Neuron 77(3), 2013)。 近期研究指出ipRGC能藉由某種未知的機制影響視網膜其他種類的細胞。了解視神經細胞如何與視網膜溝通，能使我們對複雜的神經網路與其形成機制有更深一層的了解。 藉由基因標記的方式，我們注意到部分感光視神經細胞具有視網膜內的軸突分枝。這些軸突分枝不同於走向視盤（optic disc）的主要軸突，而是回到內叢狀層（inner plexiform layer, IPL），即雙極細胞與無軸突細胞向視神經細胞傳遞訊息的突觸層。我們假設感光視神經細胞能夠藉由視網膜內的軸突分枝，向視網膜傳達周遭的亮度訊息，並以此回饋機制調控視網膜的感光功能。為了確認感光視神經細胞軸突分枝的生理功能，並且瞭解這個新發現的回饋性神經迴路，在此計畫中我們將專注於以下兩個目標： （1）確定感光神經細胞對視網膜的輸出功能。 （2）辨識具視網膜內軸突分枝感光視神經細胞及其種類。<br> Abstract: Light detection in mammals has been classically described as uni-directional signaling pathway inside the retina. The classical photoreceptor rods and cones detect photon and transmit the light information to bipolar cells which synapse on retinal ganglion cells (RGCs), while horizontal cells and amacrine cells provide lateral computation to increase detection gain and contrast. As the only output neuron in the retina, RGCs innervate various targets in the brain and typically do not provide feedback signal through axon collaterals back to the retina. A small population of RGCs, which named intrinsically photosensitive retinal ganglion cells (ipRGCs), can detect light directly by expressing photo-pigment melanopsin. According to their genetic expression pattern and morphological properties, ipRGCs can be divided into several different populations which form independent mosaic (Neuron 77(3), 2013) and control distinct functions (Nature 476, 2011). Recent evidences suggest that ipRGC could influence the physiological function of other types of neuron in the retina through an unknown mechanism. Thus, understanding of how does RGC communicate within the retina could provide us more insight on the complex neuronal circuitry in the nerve system. By utilizing the genetic labeling method, we found that some ipRGCs possess intra-retinal axon collaterals. There axon collaterals branched out from the main axon that goes toward optic disc, and innervate back to the inner plexiform layer where RGC receive synaptic input from bipolar cells and amacrine cells. We hypothesis that intra-retinal axon collaterals from ipRGCs could provide ambient irradiant information in the feedback manner to modulate the light detection function of the retina. To determine the physiological function of the intra-retinal axon collaterals from ipRGC and to understand the novel feedback connection circuitry, we will focus on two specific aims in this proposal: (1) Determine the functional output circuitry of ipRGCs within the retina. (2) Characterize the identity of ipRGCs with intra-retinal collaterals.