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bioRxiv · 10.1101/542928

Developmental time course of SNAP-25 isoform regulation of hippocampal long-term synaptic plasticity and hippocampus-dependent learning

Gopaul, K. R.·Irfan, M.·Miry, O.·Vose, L. R.·Moghadam, A. A.·Hökfelt, T.·Bark, C.·Stanton, P. K.
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Abstract

SNAP-25 is essential in activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During development and adulthood, SNAP-25 appears to have differential influences on long- and short-term synaptic plasticity in the hippocampus. The involvement of SNAP-25 in this process may be altered by two different splice variants expressed in adolescences versus adulthood in hippocampal neurons. This study suggests that the adolescent isoform, SNAP-25a can contribute to developmental regulation of the expression of LTD and LTP. In mice deficient in SNAP-25b, the adult isoform, Schaffer collateral-CA1 synapses showed slower release kinetics, reduced initial release probabilities, decreased LTP and enhanced LTD at 1 month. By 4 months of age, when mice have fully developed in the absence of SNAP-25b, the gene targeted mice appear to have compensated for the lack of the adult SNAP-25b isoform. Moreover, hippocampal-dependent training reversed reductions in LTP, but not LTD, seen at 1 month. In 4 month old adult mice, training prevented the compensatory reversal of LTD that had been observed prior to training. These findings support the hypothesis that immature SNAP-25a plays a strong role in the expression of plasticity at Schaffer collateral-CA1 synapses in adolescent mice, but compensatory mechanisms that reverse alterations in synaptic plasticity once mice reach adulthood.

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Gopaul, K. R., Irfan, M., Miry, O., Vose, L. R., Moghadam, A. A., Hökfelt, T., Bark, C., Stanton, P. K.. 2019-02-06. Developmental time course of SNAP-25 isoform regulation of hippocampal long-term synaptic plasticity and hippocampus-dependent learning. https://doi.org/10.1101/542928

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