%A Timofeeva,Yulia %A Volynski,Kirill %D 2015 %J Frontiers in Cellular Neuroscience %C %F %G English %K Synaptic Transmission,Synaptic Vesicles,short term plasticity,Calcium Channels,modelling biological systems %Q %R 10.3389/fncel.2015.00239 %W %L %M %P %7 %8 2015-July-01 %9 Original Research %+ Dr Kirill Volynski,University College London,UCL Institute of Neurology,London,United Kingdom,k.volynski@ucl.ac.uk %# %! Short-term facilitation via calmodulin dislocation %* %< %T Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation %U https://www.frontiersin.org/articles/10.3389/fncel.2015.00239 %V 9 %0 JOURNAL ARTICLE %@ 1662-5102 %X Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca2+ buffers that shape [Ca2+] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca2+ faster than any other characterized endogenous neuronal Ca2+ buffer. Direct effects of calmodulin on fast presynaptic Ca2+ dynamics and vesicular release however have not been studied in detail. Using experimentally constrained three-dimensional diffusion modeling of Ca2+ influx–exocytosis coupling at small excitatory synapses we show that, at physiologically relevant concentrations, Ca2+ buffering by calmodulin plays a dominant role in inhibiting vesicular release and in modulating short-term synaptic plasticity. We also propose a novel and potentially powerful mechanism for short-term facilitation based on Ca2+-dependent dynamic dislocation of calmodulin molecules from the plasma membrane within the active zone.