Regulation of Endocytosis at a Ribbon-Type Synapse

描述（由申请人提供）：神经元之间快速持续的化学传递需要突触囊泡与质膜融合后再循环释放递质。内吞作用是神经元将融合的囊泡膜重新内化的过程，是这个循环过程的第一个重要步骤。尽管它在维持突触囊泡的可用池和平衡突触前末端与胞吐过程中增加的膜的大小方面具有明显的必要性，但对胞吞作用知之甚少。在神经系统中尤其如此。提出的研究旨在从生理学的角度来表征内吞作用，使用来自金鱼视网膜的单个突触前双极细胞终端的膜电容测量。该项目的具体目的是：1)表征神经递质对胞吞动力学的影响；2)确定磷酸酶抑制对突触前末端胞吞作用的影响；3)确定正在进行的胞吞和胞吞过程中膜的添加和回收之间的定量关系。测量视网膜切片完整双极细胞的内吞作用。该结果有望为神经元突触前信号调节提供基础认识，并进一步阐明视网膜双极细胞的功能特征及其在视觉信号转导中的作用。

DESCRIPTION (provided by applicant): Rapid and continuous chemical transmission between neurons requires that synaptic vesicles be recycled after fusing with the plasma membrane to release transmitter. Endocytosis, the process by which neurons reinternalize fused vesicular membrane, is the first essential step in this recycling process. Despite its clear necessity in maintaining an available pool of synaptic vesicles and balancing the size of a presynaptic terminal against membrane added during exocytosis, very little is known about endocytosis. This is especially true in neuronal systems. The proposed study seeks to characterize endocytosis from a physiological perspective using membrane capacitance measurements of single presynaptic bipolar cell terminals from the goldfish retina. The specific aims of this project are: 1) To characterize the effect of neurotransmitters on the kinetics of endocytosis, 2) To determine the effect of phosphatase inhibition on endocytosis in the presynaptic terminal, 3) To determine the quantitative relationship between membrane addition and retrieval during ongoing exocytosis and endocytosis. To measure endocytosis in the intact bipolar cells of a retinal slice. The results are expected to provide fundamental insight about presynaptic signal modulation in neurons and further elucidate the functional characteristics of retinal bipolar cells and their role in visual signal transduction.