Synaptic Mechanisms in Retina

描述(申请人提供)：双极细胞将信息从光感受器传递到无长突细胞和神经节细胞。这些中间神经元不仅将视觉信息从视网膜远端传递到近端，而且还对其进行分解。其中一些分解发生在双极细胞的树突中，产生开关的双极细胞或瞬时和持续的双极细胞。但到达视网膜近端的信息在离开双极细胞轴突终末时可能会进一步分解。这项提议的目标是研究双极细胞输出突触的这种分解。其基本原理是双极细胞亚型编码关于视觉场景的特定信息。假设是多种机制控制双极细胞输出突触，这有助于信息分解。模型是无长突细胞和神经节细胞整合了一组双极细胞输出，这些输出是由轴突终末的突触前参数塑造的。这项建议的第一个具体目的是研究突触前钙通道亚型在视觉信息传递中的功能。第二个具体目的是研究自身受体反馈和无长突细胞反馈在双极细胞递质释放中的作用。假设反馈对介导递质释放的不同钙通道有不同的影响。第三个具体目标将是确定大电导(BK)通道在双极细胞突触的作用，以及钙通道亚型是否受到不同程度的影响。最终的具体目标将评估内部钙储存在调节双极细胞递质释放方面的功能。它将检验这样的假设，即体内钙促进释放，但不诱导递质释放。这些机制在建立到达神经节细胞的视觉信息方面的作用将被探索。总体而言，这些实验旨在确定双极细胞释放机制的光谱，以及它们如何确定用于编码视觉的视觉通道。

DESCRIPTION (provided by applicant): Bipolar cells convey information from photoreceptors to amacrine and ganglion cells. These interneurons not only relay visual information from distal to proximal retina, but also decompose it. Some of this decomposition occurs in the dendrites of bipolar cells, creating ON and OFF bipolar cells or transient and sustained bipolar cells. But the information reaching the proximal retina is probably further decomposed as it leaves the bipolar cell axon terminal. The objectives of this proposal are to examine this decomposition at the output synapses of bipolar cells. The rationale is that bipolar cell subtypes encode specific information about the visual scene. The hypothesis is that a variety of mechanisms control the bipolar cell output synapse and that this contributes to the information decomposition. The model is that amacrine cells and ganglion cells integrate an array of bipolar cell outputs which are shaped by presynaptic parameters at the axon terminal. The first specific aim of this proposal is to examine the function of subtypes of presynaptic calcium channels in the relay of visual information. The second specific aim will examine the function of autoreceptor feedback and amacrine cell feedback on bipolar cell transmitter release. The hypothesis is that the feedback has different effects on the various calcium channels that mediate transmitter release. The third specific aim will be to determine the effect of large conductance (BK) channels at the bipolar cell synapse and whether calcium channels subtypes are differentially affected. The final specific aim will evaluate the function of internal calcium stores in modulating bipolar cell transmitter release. It will test the hypothesis that internal calcium potentiates release but does not induce transmitter release. The role of these mechanisms in establishing the visual information reaching the ganglion cell will be explored. Overall, the experiments are designed to determine the spectrum of bipolar cell release mechanisms and how they determine the visual channels used to encode vision.