Function of Basal Synapses at Mammalian Photoreceptors

哺乳动物感光器基底突触的功能

• 批准号: 8403032
• 负责人: Steven H DeVries
• 金额: $ 34.77万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8403032
• 关键词: AMPA Receptors; Address; Affect; Amacrine Cells; Binding; Cells; Characteristics; Cleaved cell; Critical Pathways; Diffusion; Disease; Employee Strikes; Frequencies; Glutamate Receptor; Glutamate Transporter; Glutamates; Goals; Grant; Implant; Kainic Acid Receptors; Kinetics; Light; Lighting; Location; Mediating; Modeling; Movement; Mus; Pathway interactions; Pharmacology; Photoreceptors; Physiologic pulse; Play; Process; Property; Relative (related person); Retina; Retinal Cone; Role; Signal Transduction; Simulate; Site; Slice; Spermophilus; Stem cells; Structure; Synapses; Synaptic Transmission; Testing; Vision; Visual Perception; Work; cell type; desensitization; ganglion cell; kainate; photoreceptor degeneration; postsynaptic; presynaptic; receptor; research study; response; retinal rods; synaptic function; transmission process; uptake; visual process; visual processing; voltage; voltage clamp

This study addresses the relationship between the specialized structure of the mammalian cone photoreceptor synapse and signaling in postsynaptic bipolar cell pathways that are critical for visual perception. Cone photoreceptors mediate vision under conditions of bright illumination and use glutamate as their transmitter. A cone contacts two functional classes of bipolar cells, On and Off, which have different glutamate receptors that cause them to depolarize (i.e., signal) either at light-on or light-off, respectively. Each functional class of bipolar cell is further subdivided into 4-5 anatomical subtypes (e.g., b2, b3, b7). Recent work has shown that the different anatomical subtypes of Off bipolar cells express different types of glutamate receptors (AMPA or kainate), make different numbers of contacts with a cone terminal, and contact the cone terminal at distinct distances from transmitter release sites. The differences in transmitter diffusion distance, contact number, and receptor type suggest that each subtype of Off bipolar cell could process a different component of the cone signal. The main goal of this project is to determine the properties of the signals in the different subtypes of Off bipolar cells, and to relate those properties to the structure and pharmacology of the synapse. Transmission at the cone to Off bipolar cell synapse will be studied by simultaneously voltage clamping a presynaptic cone and a postsynaptic bipolar cell in slices from the cone dominant retina of the ground squirrel. The aim of the first set of experiments is to test the hypothesis that the b2 cell synapse is specialized to transmit high frequency fluctuations in cone voltage, and examine the underlying mechanisms. Specific experiments will a) determine how the amplitude of the transient depolarization at light-off varies with light pulse duration and b) use temporal flicker to determine the frequencies best transmitted by cone to Off bipolar cell synapses. The aim of the second set of experiments is to test the hypothesis that the gain of steady synaptic transmission is different at cone to b3 and b7 cell synapses. Specific experiments will determine how cone contact number and receptor desensitization affect steady synaptic gain. The aim of the third set of experiments is to test the hypothesis that cone glutamate transporters play only a small role in controlling the cleft glutamate concentration. Specific experiments will determine the extent to which ground squirrel cones recapture released glutamate and determine the locations of glutamate transporters relative to ribbon release sites.

这项研究涉及哺乳动物锥光受体的专业结构之间的关系 突触后双极细胞通路中的突触和信号对于视觉感知至关重要。锥体 光感受器在明亮照明条件下介导视力，并使用谷氨酸作为发射机。一个 锥接触两种功能性类别的双极细胞，开关，它们具有不同的谷氨酸受体 使它们分别在轻on或轻开点处去极化（即信号）。每个功能类别 将双极细胞进一步细分为4-5解剖亚型（例如B2，B3，B7）。最近的工作表明 双极细胞的不同解剖亚型表达不同类型的谷氨酸受体（AMPA或 海藻酸盐），与锥端进行不同数量的接触，并以不同的方式与锥端接触 距发射器释放位点的距离。发射机扩散距离，接触数和 受体类型表明，双极细胞的每个亚型都可以处理锥体的不同成分 信号。该项目的主要目标是确定OFF的不同子类型中信号的属性 双极细胞，并将这些特性与突触的结构和药理学联系起来。传输在 通过同时夹紧突触前锥和 从地松鼠的圆锥视网膜中的切片中的突触后双极细胞。第一个目的 一组实验是测试B2细胞突触专门发射高频的假设 锥电压的波动，并检查潜在的机制。具体实验将a）确定 轻脉冲持续时间和b）使用时间上的瞬时去极化的幅度如何变化 闪烁以确定锥体最佳传输的频率以关闭双极细胞突触。目的 第二组实验是测试以下假设：稳定突触传播的增益在 锥到B3和B7细胞突触。特定的实验将确定锥接触数量和受体如何 脱敏会影响稳定的突触增益。第三组实验的目的是检验假设 该锥形谷氨酸转运蛋白在控制谷氨酸裂解浓度中仅起着很小的作用。具体的 实验将确定地松鼠锥捕获的程度释放谷氨酸和 确定相对于色带释放位点的谷氨酸转运蛋白的位置。