Regulation of Endocytosis at a Ribbon-Type Synapse

描述(申请人提供)：神经元之间快速和持续的化学传输要求突触小泡与质膜融合后回收，以释放递质。内吞作用是神经元将融合的囊泡膜重新内化的过程，是这个循环过程中的第一个基本步骤。尽管它在维持可用的突触小泡池和平衡突触前终末的大小和胞吐过程中增加的膜的大小方面显然是必要的，但人们对内吞作用知之甚少。这在神经系统中尤其如此。这项拟议的研究试图通过对金鱼视网膜单个突触前双极细胞终末的膜电容测量，从生理学角度表征内吞作用。本项目的具体目标是：1)表征神经递质对内吞作用动力学的影响，2)确定磷酸酶抑制对突触前终末内吞作用的影响，3)确定正在进行的胞吞和胞吐过程中膜添加和回收之间的定量关系。测量视网膜切片中完整的双极细胞的内吞作用。这一结果有望为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提供对神经元突触前信号调制的基本认识。

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.