Tet2 Knockout May Lead to Selective Memory Enhancement

Memory is intimately tied to identity. This makes diseases that impact learning and memory particularly devastating. In order to better treat these disorders and diseases in the future, the mechanisms behind memory must be deciphered. It has been established that when learning occurs epigenetic modifications, specifically methyl marks, are placed on our DNA to store that memory for future recollection. Memories are directly stored in a network of neurons called an engram. The Ten Eleven Translocation (Tet) family of enzymes are methyl oxidases, which remove methyl marks from DNA, resulting in forgetting. Tet2 is one of these Tet enzymes that is of particular interest because it functions differently from the other Tet enzymes in that it does not bind directly to the DNA. It is hypothesized that memories are encoded in engrams which can be degraded over time, because of TET2. This hypothesis will be interrogated using transgenic mice with conditional Tet2 knockouts. These mice will be put through a battery of behavioral paradigms to establish a baseline, before general memory enhancement and single memory enhancement will be attempted. Engram mapping will also be employed to visualize the network of neurons involved in storing specific memories. Finally, bioinformatics will be utilized to determine where Tet2 knockout leads to differential methylation in order to better understand why its knockout leads to memory enhancement