AMPA glutamate receptors (AMPARs) are the primary mediators of excitatory synaptic communication in the brain. Emerging evidence indicates that the nervous system regulates AMPARs as a means of altering synaptic strength and excitability. It is widely accepted that long-term memories form following modifications of neuronal synapses and synaptic strength. Recent studies demonstrate that maintaining a stable number of AMPARs at the synapses is critical for memories to persist. Scientists of the EU-funded MEMORY PERSISTENCE (Molecular mechanisms of memory persistence) project wished to delineate the mechanisms that regulate AMPARs at synapses. The rationale was to understand how memories persist or get forgotten. Towards this goal, researchers investigated various proteins implicated in the trafficking of AMPARs. Their experimental plan involved the reduction of the endogenous levels of BRAG2 and PICK1, molecules involved in the internalisation and degradation of AMPAR, respectively. To evaluate the impact of these manipulations on the memory of rats, they subjected them to a task that involved learning the location of certain objects in an open field. Results showed that PICK1 knockdown did not affect memory acquisition and persistence, suggesting that PICK1-mediated AMPAR trafficking might not be involved in the loss of long-term memory. BRAG2 knockdown did not affect memory acquisition when memory was tested one day after the end of training. Additional experiments suggested that the interaction of BRAG2 and AMPARs mediated the natural decay of long-term memories. Collectively, the results of the current study provided fundamental information towards the understanding of memory persistence and loss. BRAG2 emerged as an attractive target for future studies in the field, and for the treatment of cognitive disorders characterised by pathological memory loss.
Memory, AMPA receptor, synapse, MEMORY PERSISTENCE, BRAG2