New research published in Cell Reports demonstrates that a molecule best known for its role as an axon guidance cue in the developing brain called netrin-1 plays a critical role in the strengthening of connections, called synapses, between neurons in the adult brain. This strengthening of connections, called long-term potentiation was demonstrated to require netrin-1in a brain area called the hippocampus, associated with memory formation.
Stephen Glasgow and colleagues showed that activated neurons secrete netrin-1, which then binds to receptors on their surface. This in turn triggers the dynamic recruitment of a class of excitatory receptors, called AMPA receptors to synapses. The increase in the number of AMPA receptors promotes the maturation of immature synapses, and strengthens existing synapses.
This work shows that guidance cues like netrin-1, which have been studied extensively in the developing nervous system, continue to contribute in the adult brain. Importantly, they can rapidly modify and strengthen connections in the brain through addition of receptors.
View the original research paper (open access)
Stephen D. Glasgow, Simon Labrecque, Ian V. Beamish, Sarah Aufmkolk, Julien Gibon, Dong Han, Stephanie N. Harris, Paul Dufresne, Paul W. Wiseman, R. Anne McKinney, Philippe Séguéla, Paul De Koninck, Edward S. Ruthazer, Timothy E. Kennedy
Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.
Cell Rep. 2018 Oct 2;25(1):168-182.e6.
