Synaptic transmission in the rod pathway of the mammalian retina

描述（由申请人提供）：该提案将支持对哺乳动物视网膜杆状通路中杆状双极-无突细胞突触信号可重复性、时间和动态范围的突触前和突触后机制的研究。这项研究的长期目标是了解视觉信息是如何通过视网膜神经元之间的突触相互作用编码的。三个特定的目标将解决使用电生理记录从突触耦合神经元在视网膜切片准备。具体目的1研究可重复性的突触前基础。关于突触前钙通道的动力学特性、视网膜特异性Cav1.4及其相对于活性区释放位点的位置允许突触前膜电位的变化通过突触可靠地传递的假设将被测试。具体目标2将研究控制杆状双极细胞末端神经递质释放时间的突触前机制，并研究构成释放机制的蛋白质的活性依赖性调节改变胞吐动力学的假设。具体目标3将检查突触后机制控制突触的动态范围。在活动依赖性突触抑制过程中，All膜上电压门控的钠和钾通道放大小突触传导并限制突触动态范围变化的假设将得到解决。总之，这些特定的目标将有助于阐明在视觉处理过程中允许视网膜突触正常功能的机制。这是了解病理状态下影响视力的视网膜功能改变的必要的第一步。特别是，由于Cav1.4突变是导致x连锁不完全先天性静止性夜盲症的原因，了解这些通道在突触传递中正常发挥的作用可能有助于深入了解这种疾病。

DESCRIPTION (provided by applicant): This proposal will support investigation of pre- and postsynaptic mechanisms contributing to the reproducibility, timing, and dynamic range of signaling at the rod bipolar-All amacrine cell synapse in the rod pathway of the mammalian retina. The long-term goal of this research is to understand how visual information is encoded by synaptic interactions between retinal neurons. Three specific aims will be addressed using electrophysiological recordings from synaptically coupled neurons in a retinal slice preparation. Specific aim 1 investigates the presynaptic basis of reproducibility. The hypothesis that the kinetic properties of the presynaptic calcium channel, the retina-specific Cav1.4, and its placement relative to release sites in the active zone allow changes in presynaptic membrane potential to be transmitted reliably by the synapse will be tested. Specific aim 2 will examine presynaptic mechanisms that control the timing of neurotransmitter release from rod bipolar cell terminals and investigate the hypothesis that activity-dependent modulation of the proteins composing the release machinery alters the kinetics of exocytosis. Specific aim 3 will examine postsynaptic mechanisms controlling the dynamic range of the synapse. The hypothesis that voltage-gated sodium and potassium channels in the All membrane act to amplify small synaptic conductances and limit changes in the dynamic range of the synapse during activity-dependent synaptic depression will be addressed. Together, these specific aims will serve to elucidate the mechanisms that permit the normal function of retinal synapses during visual processing. This is a necessary first step in understanding altered retinal function in pathological states affecting vision. In particular, as mutations in Cav1.4 are responsible for X-linked incomplete congenital stationary night blindness, understanding the role that these channels play normally in synaptic transmission may provide insight into this disease.