Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning
Cell Biology and Anatomy
SNAP-25 is essential to activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During early development and adulthood, SNAP-25 appears to have differential influences on short- and long-term synaptic plasticity. The involvement of SNAP-25 in these processes may be different at hippocampal and neocortical synapses because of the presence of two different splice variants, which are developmentally regulated. We show here that the isoform SNAP-25a, which is expressed first developmentally in rodent brain, contributes to developmental regulation of the expression of both long-term depression (LTD) and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the hippocampus. In one month old mice lacking the developmentally later expressed isoform SNAP-25b, Schaffer collateral-CA1 synapses showed faster release kinetics, decreased LTP and enhanced LTD. By four months of age, SNAP-25b-deficient mice appeared to have compensated for the lack of the adult SNAP-25b isoform, now exhibiting larger LTP and no differences in LTD compared to wild type mice. Interestingly, learning a hippocampus-dependent task reversed the reductions in LTP, but not LTD, seen at one month of age. In four month old adult mice, learning prevented the compensatory up-regulation of LTD that we observed prior to training. These findings support the hypothesis that SNAP-25b promotes stronger LTP and weakens LTD at Schaffer collateral-CA1 synapses in young mice, and suggest that compensatory mechanisms can reverse alterations in synaptic plasticity associated with a lack of SNAP-25b, once mice reach adulthood.
Gopaul, K. R., Irfan, M., Miry, O., Vose, L. R., Moghadam, A., Subah, G., Hökfelt, T., Bark, C., & Stanton, P. K. (2020). Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning. International Journal of Molecular Sciences, 21 (4), 1448-1448. https://doi.org/10.3390/ijms21041448