Functional development of signal transmission at cone photoreceptor ribbon synapses in mouse retina

光感受器是一种特殊的感觉神经元，它将光信号转化为电信号，并进一步转化为化学信号。为了确保信号以最高保真度传递到突触后水平细胞和双极细胞，光感受器配备了所谓的带状突触，这种突触专门用于谷氨酸的快速和高通量分级释放。对光感受器突触机制的生理特性的理解是视觉神经科学的核心问题。在提议的项目中，我将采用电刺激水平视网膜切片中的光感受器来触发突触囊泡释放，这是我们实验室开发的一种技术。电刺激结合水平细胞的膜片钳记录将使我能够研究小鼠视网膜感光带突触的关键生理特性的出生后发育。我将分析张力和相位诱发的突触囊泡释放，测量突触囊泡释放和补充的动力学，确定容易释放的突触囊泡池大小，并测量贴片钳锥光感受器中的突触前Ca2+电流。此外，我将研究突触超微结构在出生后发育过程中的变化，以便将带状突触功能与突触结构联系起来。本研究结果将建立光感受器带突触发育过程中结构与功能之间的关系，从而更好地了解成熟哺乳动物视网膜中光感受器带突触的生理和病理生理。

Photoreceptors are specialized sensory neurons that transduce light signals into electrical and further into chemical signals. To ensure signal transmission with highest fidelity to postsynaptic horizontal and bipolar cells, photoreceptors are equipped with a so-called ribbon synapse, a synapse that is specialized for the fast and high-throughput graded release of glutamate. The understanding of the physiological properties of the synaptic machinery of photoreceptors is a central issue in visual neuroscience. In the proposed project, I will employ electric stimulation of photoreceptors in horizontal retinal slices to trigger synaptic vesicle release, a technique developed in our laboratory. Electric stimulation in combination with patch-clamp recording from horizontal cells will allow me to investigate the postnatal development of key physiological properties of photoreceptor ribbon synapses in mouse retina. I will analyse both tonic and phasic evoked synaptic vesicle release, measure the kinetics of synaptic vesicle release and replenishment, determine the readily releasable synaptic vesicle pool size, and measure presynaptic Ca2+ currents in patch clamped cone photoreceptors. In addition, I will study the changes in synaptic ultrastructure during postnatal development in order to correlate ribbon synaptic function with synaptic structure. The results of this study will establish the relationship between structure and function during photoreceptor ribbon synaptic development, enabling a better understanding of the physiology and pathophysiology of photoreceptor ribbon synapses in the mature mammalian retina.