[PDF][PDF] Dynamic control of synaptic vesicle replenishment and short-term plasticity by Ca2+-calmodulin-Munc13-1 signaling

N Lipstein, T Sakaba, BH Cooper, KH Lin, N Strenzke… - Neuron, 2013 - cell.com
N Lipstein, T Sakaba, BH Cooper, KH Lin, N Strenzke, U Ashery, JS Rhee, H Taschenberger
Neuron, 2013cell.com
Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-
frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held,
repetitive activity eventually results in short-term synaptic depression, which is in part due to
the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by Ca 2+-
dependent vesicle replenishment, but the molecular mechanisms of this replenishment are
largely unknown. We studied calyces of Held in knockin mice that express a Ca 2+ …
Summary
Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held, repetitive activity eventually results in short-term synaptic depression, which is in part due to the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by Ca2+-dependent vesicle replenishment, but the molecular mechanisms of this replenishment are largely unknown. We studied calyces of Held in knockin mice that express a Ca2+-Calmodulin insensitive Munc13-1W464R variant of the synaptic vesicle priming protein Munc13-1. Calyces of these mice exhibit a slower rate of synaptic vesicle replenishment, aberrant short-term depression and reduced recovery from synaptic depression after high-frequency stimulation. Our data establish Munc13-1 as a major presynaptic target of Ca2+-Calmodulin signaling and show that the Ca2+-Calmodulin-Munc13-1 complex is a pivotal component of the molecular machinery that determines short-term synaptic plasticity characteristics.
cell.com