Departments of Neurobiology and Behavior andSUNY Eye Institute, Syracuse, NY 13202.
Departments of Neurobiology and Behavior andSUNY Eye Institute, Syracuse, NY 13202Ophthalmology, Stony Brook University, Stony Brook, NY 11794-5230; and
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8655-60. doi: 10.1073/pnas.1323962111. Epub 2014 May 27.
Ribbon synapses of photoreceptor cells and second-order bipolar neurons in the retina are specialized to transmit graded signals that encode light intensity. Neurotransmitter release at ribbon synapses exhibits two kinetically distinct components, which serve different sensory functions. The faster component is depleted within milliseconds and generates transient postsynaptic responses that emphasize changes in light intensity. Despite the importance of this fast release for processing temporal and spatial contrast in visual signals, the physiological basis for this component is not precisely known. By imaging synaptic vesicle turnover and Ca(2+) signals at single ribbons in zebrafish bipolar neurons, we determined the locus of fast release, the speed and site of Ca(2+) influx driving rapid release, and the location where new vesicles are recruited to replenish the fast pool after it is depleted. At ribbons, Ca(2+) near the membrane rose rapidly during depolarization to levels >10 µM, whereas Ca(2+) at nonribbon locations rose more slowly to the lower level observed globally, consistent with selective positioning of Ca(2+) channels near ribbons. The local Ca(2+) domain drove rapid exocytosis of ribbon-associated synaptic vesicles nearest the plasma membrane, accounting for the fast component of neurotransmitter release. However, new vesicles replacing those lost arrived selectively at the opposite pole of the ribbon, distal to the membrane. Overall, the results suggest a model for fast release in which nanodomain Ca(2+) triggers exocytosis of docked vesicles, which are then replaced by more distant ribbon-attached vesicles, creating opportunities for new vesicles to associate with the ribbon at membrane-distal sites.
视网膜中的光感受器细胞和二级双极神经元的带状突触是专门用来传递编码光强度的渐变信号的。神经递质在带状突触的释放表现出两种动力学上不同的成分，它们服务于不同的感觉功能。较快的成分在几毫秒内耗尽，并产生短暂的突触后反应，强调光强度的变化。尽管这种快速释放对于处理视觉信号的时间和空间对比度非常重要，但这种成分的生理基础尚不清楚。通过在斑马鱼双极神经元中单个带状突触中成像突触小泡周转和 Ca(2+)信号，我们确定了快速释放的位置、驱动快速释放的 Ca(2+)内流的速度和位置，以及在快速池耗尽后新囊泡被招募来补充快速池的位置。在带状突触中，在去极化过程中，靠近膜的 Ca(2+)迅速升高到 >10 µM 的水平，而在非带状突触位置的 Ca(2+)则缓慢升高到观察到的全局较低水平，这与 Ca(2+)通道在带状突触附近的选择性定位一致。局部 Ca(2+)域驱动最靠近质膜的带状相关突触小泡的快速胞吐作用，这解释了神经递质释放的快速成分。然而，取代那些丢失的囊泡的新囊泡选择性地到达带状突触的相反极，远离膜。总的来说，这些结果表明了一种快速释放的模型，其中纳米域 Ca(2+)触发停靠囊泡的胞吐作用，然后由更远的带状附着囊泡取代，为新囊泡在膜远侧部位与带状突触结合创造机会。
