Nonequivalent release sites govern synaptic depression

Hua Wen, Matthew J. McGinley, Gail Mandel, Paul Brehm

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Synaptic depression is prominent among synapses, but the underlying mechanisms remain uncertain. Here, we use paired patch clamp recording to study neuromuscular transmission between the caudal primary motor neuron and target skeletal muscle in zebrafish. This synapse has an unusually low number of release sites, all with high probabilities of release in response to low-frequency stimulation. During high-frequency stimulation, the synapse undergoes shortterm depression and reaches steady-state levels of transmission that sustain the swimming behavior. To determine the release parameters underlying this steady state, we applied variance analysis. Our analysis revealed two functionally distinct subclasses of release sites differing by over 60-fold in rates of vesicle reloading. A slow reloading class requires seconds to recover and contributes to depression onset but not the steady-state transmission. By contrast, a fast reloading class recovers within tens of milliseconds and is solely responsible for steady-state transmission. Thus, in contrast to most current models that assign levels of steady-state depression to vesicle availability, our findings instead assign this function to nonuniform release site kinetics. The duality of active-site properties accounts for the highly nonlinear dependence of steady-state depression levels on frequency.

Original languageEnglish (US)
Pages (from-to)E378-E386
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Jan 19 2016


  • Multinomial analysis
  • Neuromuscular
  • Synaptic plasticity
  • Synaptic vesicle
  • Zebrafish

ASJC Scopus subject areas

  • General


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