A stabilising influence: Integrins in regulation of synaptic plasticity.
McGeachie AB, Cingolani LA, Goda Y.
Hebbian synaptic plasticity, such as hippocampal long-term potentiation (LTP), is thought to be important for particular types of learning and memory. It involves changes in the expression and activity of a large array of proteins, including cell adhesion molecules. The integrin class of cell adhesion molecules has been extensively studied in this respect, and appear to have a defined role in consolidating both structural and functional changes brought about by LTP. With the use of integrin inhibitors, it has been possible to identify a critical time window of several minutes after LTP induction for the participation of integrins in LTP. Altering the interactions of integrins with their ligands during this time compromises structural changes involving actin polymerisation and spine enlargement that could be required for accommodating new AMPA receptors (AMPARs). After this critical window of structural remodelling and plasticity, integrins "lock-in" and stabilise the morphological changes, conferring the requisite longevity for LTP. Genetic manipulations targeting integrin subtypes have helped identify the specific integrin subunits involved in LTP and correlate alterations in plasticity with behavioural deficits. Moreover, recent studies have implicated integrins in AMPAR trafficking and glycine receptor lateral diffusion, highlighting their multifaceted functions at the synapse.