Our group discovered that the natural loss of long-term memory over time involves the activity-dependent removal of GluA2/AMPARs from post-synaptic sites. Currently, we are studying cellular signalling pathways involved in this active decay process, focussing on known proteins interacting with GluA2/AMPARs at post-synaptic compartments, and the relevant signalling events.

The removal of GluA2/AMPARs from post-synaptic membranes to reduce synaptic strength is brought about by dynamin- and clathrin-mediated endocytosis. Removed and internalized AMPARs undergo endosomal sorting processes that either recycle receptors back into the plasma membrane or direct them to degradation by the lysosomal pathway. These trafficking processes rely on the interaction of the GluA2 subunit with various molecules of the post-synaptic density. We are currently exploring several candidate molecules that may be involved in this process,

We are also interested in the processes that initiate active decay, presently focussing on the role of NMDA receptors (NMDARs) because their activation generally initiates activity-dependent AMPAR trafficking during synaptic plasticity. Extending earlier findings, we recently discovered that NMDARs bidirectionally control forgetting: blocking NMDARs in the dorsal hippocampus during the memory retention interval prevents active decay of long-term memory, while enhancing NMDAR function accelerates it. We now further explore the signalling pathways controlled by NMDAR activation that underpin endogenous forgetting.