Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment

Synapsins (Syns) I and II are major synaptic vesicle (SV) proteins that function in the regulation of SV availability for release in mature neurons. Syns I/II show high level of sequence similarity and share many functions in vivo, although distinct physiological roles for the two proteins have been proposed. Both SynI-/- and SynII-/- mice have a normal lifespan, but exhibit decreased number of SVs and pronounced depression upon high frequency stimulation. Due to the Syns’ role in synaptic organization and plasticity, we studied the long-lasting effects of Syn deletion on the phenotype of SynI-/- and SynII-/- mice during aging. Both SynI-/- and SynII -/- mice displayed behavioural defects that emerged during aging and involved emotional memory in both mutants, and spatial memory in SynII-/- mice. These abnormalities were associated with neuronal loss and gliosis in the cerebral cortex and hippocampus, which were more pronounced in SynII-/- mice. The data indicate that synaptic dysfunctions associated with Syn mutations negatively modulate cognitive performance and neuronal survival during senescence.