InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Bernstein Center for Computational Neuroscience, University of Göttingen, 37073 Göttingen, Germany; Max Planck Institute for Dynamics and Self-Organization, 37077 Göttingen, Germany.
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama 359-8555, Japan.
Neuron. 2014 Sep 17;83(6):1389-403. doi: 10.1016/j.neuron.2014.08.003. Epub 2014 Sep 4.
The mechanisms underlying the large amplitudes and heterogeneity of excitatory postsynaptic currents (EPSCs) at inner hair cell (IHC) ribbon synapses are unknown. Based on electrophysiology, electron and superresolution light microscopy, and modeling, we propose that uniquantal exocytosis shaped by a dynamic fusion pore is a candidate neurotransmitter release mechanism in IHCs. Modeling indicated that the extended postsynaptic AMPA receptor clusters enable large uniquantal EPSCs. Recorded multiphasic EPSCs were triggered by similar glutamate amounts as monophasic ones and were consistent with progressive vesicle emptying during pore flickering. The fraction of multiphasic EPSCs decreased in absence of Ca(2+) influx and upon application of the Ca(2+) channel modulator BayK8644. Our experiments and modeling did not support the two most popular multiquantal release interpretations of EPSC heterogeneity: (1) Ca(2+)-synchronized exocytosis of multiple vesicles and (2) compound exocytosis fueled by vesicle-to-vesicle fusion. We propose that IHC synapses efficiently use uniquantal glutamate release for achieving high information transmission rates.
内毛细胞（IHC）带状突触中兴奋性突触后电流（EPSC）的大振幅和异质性的潜在机制尚不清楚。基于电生理学、电子和超分辨率显微镜以及建模，我们提出由动态融合孔形成的量子外排是 IHC 中神经递质释放的候选机制。建模表明，延伸的突触后 AMPA 受体簇能够产生大的量子 EPSC。记录的多相 EPSC 是由与单相 EPSC 相似的谷氨酸量触发的，并且与孔闪烁过程中囊泡的逐渐排空一致。在没有 Ca(2+)内流的情况下以及应用 Ca(2+)通道调节剂 BayK8644 时，多相 EPSC 的比例会降低。我们的实验和建模不支持 EPSC 异质性的两种最流行的多量子释放解释：（1）多个囊泡的 Ca(2+)同步外排，以及（2）由囊泡融合驱动的复合外排。我们提出，IHC 突触有效地利用量子谷氨酸释放来实现高信息传输率。
