Aim: 

A considerable number of experimental and modelling results indicate that stable, long-lasting changes in synaptic function are involved in memory formation. However, little is know about the brain function of short-lived changes in synaptic strength. Experimental evidence emerging from different sets of studies suggest that short-term plasticity (STP) is not simply a by-product of the complex regulation of longer-lasting changes in synaptic strength, but that it may have a significant role of its own in information processing.

Post-tetanic potentiation (PTP) is a widespread form of homosynapticplasticity that, together with other forms of short-term synapticenhancement (STE), is considered as one of the neural substratesof short-term memory and synaptic computation. Eventhough PTP – and other forms of STE – are generallythought to depend on the activity-dependent increase of Ca²⁺ concentration in presynaptic terminals, the downstream moleculareffectors of Ca²⁺ elevation in these plastic phenomena havebeen only partially defined.

One of the molecular effectors of PTP could be the family of the synapsins, phylogenetically conserved synapticvesicle (SV)-associated proteins that, among other functions,have been implicated in the regulation of STE, and other typesof short-term plasticity in various vertebrates and invertebrates.The biologicalactivity of these proteins is largely regulated by phosphorylationat distinct sites by multiple protein kinases, including proteinkinase A (PKA) and Ca²⁺/calmodulin-dependent kinases (CaMK)I, II and IV. Synapsins are also well known to be MAPK/Erk substrates at phylogenetically conserved sites in the N-terminal B domain.

Methods and Results: 

To study the role of phosphorylation of different synapsin domains in PTP, we took advantage of in-vitro-reconstructedgiant synapses of identified Helix pomatia neurons, which arecapable of expressing multiple forms of STE that have been characterizedpreviously. To this aim, we have clonedthe synapsin orthologue in H. pomatia (helSyn) and comparedthe effects of the selective presynaptic over-expression of eitherwild-type or domain A and domain B-mutants helSyn on the short-term plasticityof synapses between H. pomatia neurons. We have foundthat PTP at these synapses depends on the activation of CaMKsand PKA, as well as MAPK/Erk and that the presynaptic over-expression of a non-phosphorylatablesynapsin mutant acts in a dominant-negative manner by severelyimpairing PTP. Althoughboth the wild-type and mutant helSyn forms were targeted tothe synaptic compartments, the non-phosphorylatable mutant form appeared more densely packedat both synaptic and extrasynaptic sites, whereas the pseudo-phosphorylated form had a more diffuse distribution.

Conclusion: 

Together, these observationsindicate that synapsin phosphorylation-dependent changesin SV trafficking and neurotransmitter release are involvedin the expression of PTP.