Grant: Operating Grant

Many common neurological diseases are associated with memory loss. The characterization and identification of normal mechanisms that allow memories to persist has been a major goal of neuroscientists in order to target these therapeutically. Memories are believed to be stored by stable modifications in the connections between nerve cells. There are many drugs that can interfere with the formation of new memories. However, none of those drugs can modify memories once they have been created unless they are applied immediately after memory retrieval. A recent discovery has shown that a molecule called PKMzeta is crucial for maintaining long-term memories in several invertebrate and vertebrate species. If the activity of this molecule is blocked in specific brain regions, after the memory has been formed, these are erased, even when the inhibitor is given months after the initial learning. This finding indicates that memories persist because of ongoing processes in the brain. We have focus then in identifying these processes that allow memories to persist after they have been created. We demonstrated that PKMzeta is required to prevent the removal of a pool of molecules (receptors) at specific locations of the cell membrane where the neurons make contact. These receptors are responsible for the strength of the connections between neurons and without them memory cannot be expressed. The focus of this research proposal is first to identify the precise molecular pathways that control the stability of these receptors at the neuronal connections sites and therefore control the memory persistence. Secondly, we will attempt to find if these processes are modified in response to memory restore. We believe that the identification of the mechanisms that maintain memory and their dynamics will have very important implications for the treatments of memory related diseases.