Synapsins regulate use-dependent synaptic plasticity in the calyx of Held by a Ca2+/calmodulin-dependent pathway.
Synapsins are abundant synaptic-vesicle phosphoproteins that are known to regulate neurotransmitter release but whose precise function has been difficult to pinpoint. Here, we use knockout mice to analyze the role of synapsins 1 and 2 in the calyx of Held synapse, allowing precise measurements of neurotransmitter release. We find that deletion of synapsins did not induce significant changes in spontaneous release or release evoked by isolated action potentials (APs) and did not alter the size of the readily releasable vesicle pool (RRP), the kinetics of RRP depletion, or the rate of recovery of the RRP after depletion. Deletion of synapsins, however, did increase use-dependent synaptic depression induced by a high-frequency stimulus train (> or = 50 Hz). The increased depression was due to a decrease in the fraction of the RRP, whose release was evoked by APs late in the stimulus train. The effect of synapsin deletions was occluded by intracellular application of the Ca2+-chelator EGTA or of a calmodulin inhibitor. Our results show that synapsins boost the release probability during high-frequency stimulation and suggest that this effect involves Ca2+/calmodulin-dependent phosphorylation of synapsins.
Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9111, USA. jianyuan.sun@utsouthwestern.edu
Jianyuan
J
Sun
Peter
P
Bronk
Xinran
X
Liu
Weiping
W
Han
Thomas C
TC
Südhof
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D013569:Synapses / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*
D002147:Calmodulin; D016704:Synapsins; D004533:Egtazic Acid; D002118:Calcium