2010-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/710149摘要：在可以接受任何感覺輸入之前，視覺系統的發育具有一個關鍵期，而在此關鍵期中，模式化的自發性放電對視覺網路形成具有重要的影響。這個自發性的放電活動在視網膜節細胞 (retinal ganglion cell, RGC) 層具有特殊的時空特性，稱為〝retinal wave〞。之前的研究顯示adenosine在retinal wave活性的調控中扮演重要的角色。然而，關於adenosine如何在細胞層級調控此種模式化自發性活動仍未被了解。我們的初步數據顯示，在大鼠的RGC中，adenosine receptor的活化除了改變retinal wave的頻率，也改變了細胞膜的性質。我們假設上述受adenosine調控的效應可能由兩種不同機制調節，即調節SAC (starburst amacrine cell) 及RGC之間的突觸傳導，以及調節SAC及RGC細胞內的離子通道而分別改變二者之細胞膜性質。我們將利用molecular perturbation, primary culture, whole-cell patch clamp以及live time imaging回答下列問題：第一，哪一亞型的adenosine receptor調控這兩種不同的機制，而當adenosine receptor被活化時，其下游的訊息傳導層級 (signal cascade) 為何？第二，adenosine訊息如何影響傳導物質由SAC釋出而改變接收此傳導物質的RGC之反應？最後，adenosine如何去調控離子通道進而改變SAC及RGC的細胞膜性質？經由解釋這些問題，我們可以了解adenosine在調節視網膜發育中模式化自發性活動的角色，而此一認知對於神經發育之普遍機制的了解具有重要的意義。 <br> Abstract: Before any sensory input is possible, there is a critical development period during which the patterned spontaneous activity can influence development of circuits in visual system. This spontaneous activity consists of distinct spatiotemporal properties across the retinal ganglion cell (RGC) layer termed as “retinal waves”. Previous studies showed that adenosine plays an important role in regulating retinal waves activity. However, it is unknown at the cellular level how adenosine can modulate the patterned spontaneous activity. Our preliminary data showed that in addition to change wave frequency, activation of adenosine receptors also alters membrane properties in the rat RGCs. We hypothesize these two adenosine-mediated effects may be mediated by two different mechanisms, i.e. modulation of synaptic transmission between Starburst amacrine cells (SACs) and RGCs, and regulation of the ion channels underlying membrane properties in SACs and RGCs, respectively. The goal of this proposal is to elucidate how adenosine modulates the wave activity in terms of synaptic transmission and membrane properties. By combining molecular perturbation, primary culture, whole-cell patch clamp and live time imaging, we will address the following questions. First, which adenosine receptor subtypes mediate these two different mechanisms? And what is the downstream signaling cascade following activation of adenosine receptors? Second, how does adenosine signaling affect transmitter release from SACs and then change the responsiveness of RGCs, which receive the transmitters released from SACs? Last, how does adenosine modulate ion channels to alter membrane properties in SACs and RGCs, respectively? By addressing these questions, we can understand the role of adenosine in modulating the patterned spontaneous activity in the developing retina, which is potentially significant for understanding the general mechanism in neural development.腺&#33527酸視網膜波突觸傳導神經發育模式化自發性活動AdenosineRetinal wavesSynaptic transmissionNeural developmentPatterned spontaneous activity