Grant: Operating Grant

The mechanisms involved in memory storage have been intensively studied during the last decades. These investigations gave rise to the now dominant view that protein-synthesis dependent processes are required to store memories over time. Early studies demonstrating that protein-synthesis inhibitors (PSIs) disrupt memory storage when administered shortly after learning also suggested that the expression of long-term memory during a retention test is not impaired when protein-synthesis is inhibited by systemic PSI injections. Since then, memory expression has been modeled as a relatively passive readout of memory representations that does not engage the molecular, protein-synthesis dependent mechanisms engaged during learning. Mainly for this reason, little is known about the molecular events associated with memory expression. We will attempt to shed some light on this area using behavioral paradigms. Employing drugs targeting specific molecular pathways that were thought to only be involved in learning, we will challenge memory expression, and monitor changes in expression of receptors associated with memory formation. So far, we have striking results suggesting that memory expression might be mediated by rather dynamic molecular mechanisms. If the experiments proposed here confirm these findings, our current understanding of how memory is expressed would be in need for fundamental revision. The implications would not only be of theoretical nature, but would touch directly on the clinical treatment of memory related disorders. For example, the clinician may be able to control retrieval of specific memories in patients suffering from aversive, traumatic experiences, and, on the other hand, may help those who suffer from apparent amnesia, in cases where this memory loss represents a failure in the retrieval of memory that still exists but is repressed.