title: Nonequivalent release sites govern synaptic depression.
abstract: 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 short-term 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.
authors.affiliation: Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239;
authors.forename: Hua
authors.initials: H
authors.lastname: Wen
authors.affiliation: Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239;
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McGinley
authors.affiliation: Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239; Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, OR 97239 mandelg@ohsu.edu.
authors.forename: Gail
authors.initials: G
authors.lastname: Mandel
authors.affiliation: Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239;
authors.forename: Paul
authors.initials: P
authors.lastname: Brehm
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011336:Probability; D015203:Reproducibility of Results; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D015027:Zebrafish / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins
keywords: multinomial analysis; neuromuscular; synaptic plasticity; synaptic vesicle; zebrafish