Synaptic transmission in the rod pathway of the mammalian retina

哺乳动物视网膜视杆通路中的突触传递

• 批准号: 7389476
• 负责人: Joshua H Singer
• 金额: $ 33.3万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389476
• 关键词: Address; Affect; Amacrine Cells; Calcium Channel; Cells; Chromosome Pairing; Coupled; Disease; Excitatory Postsynaptic Potentials; Exocytosis; Goals; In Vitro; Investigation; Joints; Kinetics; Link; Membrane; Membrane Potentials; Mutation; Neurons; Night Blindness; Pathology; Pathway interactions; Photons; Placement; Play; Potassium Channel; Preparation; Probability; Process; Property; Proteins; Range; Rate; Rattus; Relative (related person); Reproducibility; Research; Residual state; Rest; Retina; Retinal; Role; Signal Transduction; Site; Slice; Sodium; Synapses; Synaptic Transmission; Testing; Time; Vesicle; Vision; Visual; absorption; base; insight; light intensity; neurotransmitter release; postsynaptic; presynaptic; response; retinal neuron; retinal rods; spatial relationship; synaptic depression; visual information; visual process; visual processing; voltage; Address; Affect; Amacrine Cells; Calcium Channel; Cells; Chromosome Pairing; Coupled; Disease; Excitatory Postsynaptic Potentials; Exocytosis; Goals; In Vitro; Investigation; Joints; Kinetics; Link; Membrane; Membrane Potentials; Mutation; Neurons; Night Blindness; Pathology; Pathway interactions; Photons; Placement; Play; Potassium Channel; Preparation; Probability; Process; Property; Proteins; Range; Rate; Rattus; Relative (related person); Reproducibility; Research; Residual state; Rest; Retina; Retinal; Role; Signal Transduction; Site; Slice; Sodium; Synapses; Synaptic Transmission; Testing; Time; Vesicle; Vision; Visual; absorption; base; insight; light intensity; neurotransmitter release; postsynaptic; presynaptic; response; retinal neuron; retinal rods; spatial relationship; synaptic depression; visual information; visual process; visual processing; voltage

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.

描述（由申请人提供）：该提案将支持对哺乳动物视网膜杆的杆双极性全氨酰胺细胞突触的可重复性，时机和动态信号传导的促进前和突触后机制的研究。这项研究的长期目标是了解如何通过视网膜神经元之间的突触相互作用来编码视觉信息。使用视网膜切片制剂中突触耦合神经元的电生理记录将解决三个特定的目标。特定目标1研究了重现性的突触前基础。突触前钙通道，视网膜特异性CAV1.4及其相对于活性区域中释放位点的放置的假设将通过突触可靠地通过Synapse可靠地传播突触前膜电位的变化。具体目标2将检查从杆双极细胞末端释放神经递质时间的突触前机制，并研究了组成释放机械的蛋白质的活性依赖性调节的假设改变了胞外生物的动力学。具体目标3将检查控制突触动态范围的突触后机制。将解决在活动依赖性突触抑制期间突触的动态范围的“全膜法”中电压门控钠和钾通道的假设。总之，这些特定目标将有助于阐明视觉处理过程中视网膜突触正常功能的机制。这是理解影响视力的病理状态的视网膜功能改变的必要第一步。特别是，由于CAV1.4中的突变负责X连锁的不完整的先天性固定夜间失明，因此了解这些频道在突触传播中正常发挥的作用可能会洞悉该疾病。