Dynamic Control of Synaptic Vesicle Replenishment and Short-Term Plasticity by Ca2+-Calmodulin-Munc13-1 Signaling

Noa Lipstein, Takeshi Sakaba, Benjamin H. Cooper, Kun Han Lin, Nicola Strenzke, Uri Ashery, Jeong Seop Rhee, Holger Taschenberger, Erwin Neher, Nils Brose*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 byCa2+-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

Original languageEnglish
Pages (from-to)82-96
Number of pages15
JournalNeuron
Volume79
Issue number1
DOIs
StatePublished - 10 Jul 2013

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