Differential Effect on Hippocampal Synaptic Facilitation by the Presynaptic Protein Mover

Abstract

Neurotransmitter release relies on an evolutionarily conserved presynaptic machinery. Nonetheless, some proteins occur in certain species and synapses, and are absent in others, indicating that they may have modulatory roles. How such proteins expand the power or versatility of the core release machinery is unclear. The presynaptic protein Mover/TPRGL/SVAP30 is heterogeneously expressed among synapses of the rodent brain, suggesting that it may add special functions to subtypes of presynaptic terminals. Mover is a synaptic vesicle-attached phosphoprotein that binds to Calmodulin and the active zone scaffolding protein Bassoon. Here we use a Mover knockout mouse line to investigate the role of Mover in the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse and Schaffer collateral to CA1. While Schaffer collateral synapses were unchanged by the knockout, the MFs showed strongly increased facilitation. The effect of Mover knockout in facilitation was both calcium- and age-dependent, having a stronger effect at higher calcium concentrations and in younger animals. Increasing cyclic adenosine monophosphate (cAMP) levels by forskolin equally potentiated both wildtype and knockout MF synapses, but occluded the increased facilitation observed in the knockout. These discoveries suggest that Mover has distinct roles at different synapses. At MF terminals, it acts to constrain the extent of presynaptic facilitation.