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视杆通路中视杆双极-全无长突细胞突触处信号传导的再现性、时序和动态范围做出贡献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。三个具体的目标将解决使用电生理记录从视网膜切片制备的突触耦合神经元。具体目标1研究再现性的突触前基础。突触前钙通道的动力学特性，视网膜特异性Cav1.4，其位置相对于活动区中的释放位点允许突触前膜电位的变化被可靠地传递的突触的假设将被测试。具体目标2将检查突触前机制，控制神经递质释放的时间从杆双极细胞终端和调查的假设，即活动依赖性调制的蛋白质组成的释放机制改变了动力学的胞吐作用。具体目标3将检查控制突触动态范围的突触后机制。电压门控钠和钾通道在所有膜的作用，以放大小突触电导和限制活动依赖性突触抑制过程中的突触的动态范围的变化的假设将得到解决。总之，这些具体的目标将有助于阐明机制，允许正常功能的视网膜突触在视觉处理。这是理解在影响视力的病理状态下视网膜功能改变的必要的第一步。特别是，由于Cav1.4的突变是X连锁不完全先天性静止性夜盲症的原因，因此了解这些通道在突触传递中正常发挥的作用可能会为了解这种疾病提供帮助。

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.