[Show abstract][Hide abstract] ABSTRACT: Synapsins regulate synaptic transmission by controlling the reserve pool of synaptic vesicles. Each of the three mammalian synapsin genes is subject to alternative splicing, yielding several isoforms whose roles are unknown. To investigate the function of these isoforms, we examined the synaptic effects of introducing each isoform into glutamatergic cultured hippocampal neurons from synapsin triple knock-out mice. Remarkably, we found that synapsin IIa was the only isoform that could rescue the synaptic depression phenotype of the triple knock-out mice; other isoforms examined, including the well-studied synapsin Ia isoform, had no significant effect on the kinetics of synaptic depression. The slowing of synaptic depression by synapsin IIa was quantitatively paralleled by an increase in the density of reserve pool synaptic vesicles, as measured either by fluorescent tagging of the vesicle protein synaptobrevin-2 or by staining with the styryl dye FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)-hexatrienyl)pyridinium dibromide]. Our results provide further support for the hypothesis that synapsins define the kinetics of synaptic depression at glutamatergic synapses by controlling the size of the vesicular reserve pool and identify synapsin IIa as the isoform primarily responsible for this task.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 11/2008; 28(43):10835-43. DOI:10.1523/JNEUROSCI.0924-08.2008 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One of the most remarkable properties of synapses is their ability to keep track of their history of prior activity. Information about synaptic activity is encoded in various forms of activity-dependent plasticity, both short-term forms of synaptic plasticity that last from milliseconds to minutes and long-term forms of plasticity that persist for 30 minutes or longer. Collectively, these forms of synaptic plasticity control the dynamics of neural circuit function over an incredible range of timescales and are thought to play fundamental roles in information processing by these circuits. As a result, much attention has been focused on understanding their underlying cellular and molecular mechanisms.