| First Author | Glasgow SD | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 1 | Pages | 168-182.e6 |
| PubMed ID | 30282026 | Mgi Jnum | J:270793 |
| Mgi Id | MGI:6278729 | Doi | 10.1016/j.celrep.2018.09.028 |
| Citation | Glasgow SD, et al. (2018) Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus. Cell Rep 25(1):168-182.e6 |
| abstractText | Dynamic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, but 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. Furthermore, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca(2+)-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. |
