Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.

Glasgow, S. D.; Labrecque, S.; Beamish, I. V.; Aufmkolk, S.; Gibon, J.; Han, D.; Harris, S. N.; Dufresne, P.; Wiseman, P. W.; McKinney, R. A.; Seguela, P.; De Koninck, P.; Ruthazer, E.; Kennedy, T. E.

doi:10.1101/330688

bioRxiv · 10.1101/330688

Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.

Glasgow, S. D.·Labrecque, S.·Beamish, I. V.·Aufmkolk, S.·Gibon, J.·Han, D.·Harris, S. N.·Dufresne, P.·Wiseman, P. W.·McKinney, R. A.·Seguela, P.·De Koninck, P.·Ruthazer, E.·Kennedy, T. E.

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Abstract

Dynamic trafficking of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

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Glasgow, S. D., Labrecque, S., Beamish, I. V., Aufmkolk, S., Gibon, J., Han, D., Harris, S. N., Dufresne, P., Wiseman, P. W., McKinney, R. A., Seguela, P., De Koninck, P., Ruthazer, E., Kennedy, T. E.. 2018-05-25. Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.. https://doi.org/10.1101/330688

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