Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.271742v1?rss=1 Authors: Grasskamp, A. T., Jusyte, M., McCarthy, A. W., Goetz, T. W. B., Walter, A. M. Abstract: Synaptic transmission relies on presynaptic neurotransmitter (NT) release from synaptic vesicles (SVs), and on NT detection by postsynaptic receptors. Two principal modes exist: action-potential (AP) evoked and AP-independent "spontaneous" transmission. Though universal to all synapses and essential for neural development and function, regulation of spontaneous transmission remains enigmatic. Mechanisms divergent from AP-evoked transmission were described, but are difficult to reconcile with its established function in adjusting AP-evoked transmission. By studying neurotransmission at individual synapses of Drosophila larval neuromuscular junctions (NMJs), we show a clear interdependence of transmission modes: Components of the AP-evoked NT-release machinery (Unc13, Syntaxin-1 and BRP) also predicted spontaneous transmission. Both modes were reduced when blocking voltage-gated calcium channels and engaged an overlapping pool of SVs and NT-receptors. While a small subset (~21%) of spontaneously active synapses appeared limited to this mode, most also mediated AP-evoked transmission and activity was highly correlated. Thus, by engaging overlapping molecular machinery, spontaneous transmission predicts AP-evoked transmission at single synapses. Copy rights belong to original authors. Visit the link for more info