Function of Basal Synapses at Mammalian Photoreceptors

本研究探讨哺乳动物视锥感光细胞的特化结构与 突触后双极细胞通路中的突触和信号对视觉感知至关重要。锥状 光感受器在明亮的光照条件下调节视觉，并使用谷氨酸作为其递质。一个 锥体接触两类双极细胞，开和关，它们有不同的谷氨酸受体， 使它们分别在亮起或熄灭时去极化(即，信号)。的每个功能类 双极细胞进一步细分为4-5个解剖亚型(例如，b2、b3、b7)。最近的研究表明， 不同亚型的非双极细胞表达不同类型的谷氨酸受体(AMPA或 Kainate)，与锥形端子进行不同数量的接触，并在不同的位置接触锥形端子 距离发射机投放点的距离。发射器扩散距离、接触数和 受体类型提示每种亚型的非双极细胞可以处理锥体的不同成分 信号。本项目的主要目标是确定OFF不同子类型中的信号属性 双极细胞，并将这些特性与突触的结构和药理学联系起来。传输时间： 锥体到双极细胞突触的研究将通过同时电压钳制突触前锥和 突触后双极细胞切片，取自松鼠的视锥优势视网膜。第一个的目标是 一系列实验是为了验证b2细胞突触专用于传递高频的假设。 锥体电压的波动，并研究其潜在的机制。具体的实验将确定a) 关机时的瞬时去偏振幅度如何随光脉冲持续时间变化，以及b)使用时间 闪烁以确定锥体至双极细胞突触的最佳传输频率。该计划的目的是 第二组实验是为了检验这样的假设，即稳定突触传递的增益在 锥体通向b3和b7细胞突触。具体的实验将确定锥体接触数和接收器 脱敏作用会影响稳定的突触增益。第三组实验的目的是检验这一假设 锥体谷氨酸转运体在控制裂隙谷氨酸浓度中只起到很小的作用。特定的 实验将确定松鼠视锥重新捕获释放的谷氨酸和 确定谷氨酸转运体相对于丝带释放部位的位置。

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.