Site-specific synapsin I phosphorylation participates in the expression of post-tetanic potentiation and its enhancement by BDNF.
A large amount of experimental evidence has highlighted the rapid changes in synaptic efficacy induced by high-frequency stimulation and BDNF at central excitatory synapses. We clarified the quantal mechanisms and the involvement of Synapsin I (SynI) phosphorylation in the expression of post-tetanic potentiation (PTP) and in its modulation by BDNF in mouse glutamatergic autapses. We found that PTP is associated with an elevation in the probability of release and a concomitant increase in the size of the readily releasable pool (RRP). The latter component was virtually absent in SynI knock-out (KO) neurons, which indeed displayed impaired PTP. PTP was fully rescued by the expression of wild-type SynI, but not of its dephosphomimetic mutants in the phosphorylation sites for cAMP-dependent protein kinase and Ca²⁺/calmodulin-dependent protein kinases I/II. BDNF potently enhanced PTP through a further increase in the RRP size, which was missing in SynI KO neurons. In these neurons, the BDNF-induced PTP enhancement was rescued by the expression of wild-type SynI, but not of its dephosphomimetic mutant at the mitogen-dependent protein kinase sites. The results indicate that the increase in RRP size necessary for the full expression of PTP, and its sensitivity to BDNF, involve phosphorylation of SynI at distinct sites, thus implicating SynI as an essential downstream effector for the expression of PTP and for its enhancement by BDNF.
Section of Physiology, Department of Experimental Medicine, University of Genoa and National Institute of Neuroscience, 16132 Genova, Italy.
SourceThe Journal of neuroscience : the official journal of the Society for Neuroscience 32:17 2012 Apr 25 pg 5868-79
Analysis of Variance
Brain-Derived Neurotrophic Factor
Excitatory Amino Acid Antagonists
Excitatory Postsynaptic Potentials
Gene Expression Regulation
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase Kinases
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't