The Role of PKMzeta in Memory Destabilization and Reconsolidation

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The study of memory has come a long way in identifying important molecules in the brain necessary for learning and maintaining long-term memories. One such molecule is the protein PKMzeta which is crucial for maintaining memories over time. What is unclear, however, is how PKMzeta and its memory maintenance process copes with rapid changes to memory. For instance, when certain stored (stable) memories are recalled, they become temporarily unstable only to be re-stabilized shortly thereafter. How memories destabilize on the cellular level is largely unclear but it seems likely that changes to PKMzeta may be responsible. This research will investigate the role of PKMzeta in memory destabilization and re-stabilization (or “reconsolidation”). To do so, we will use biochemistry techniques to study and manipulate auditory fear memories in rats at the protein level. Specifically, these are memories in which a rat learns that a tone predicts a footstock and subsequently shows fear behavior (“freezing”) when the tone is played. ***Evidence suggests that a decrease in the quantity of PKMzeta seems to coincide with memory destabilization. We will therefore test if production of new PKMzeta is necessary to re-stabilize the memory by blocking production of this protein specifically while the memory is destabilized. We will also test if memory destabilization requires a decrease in the quantity of PKMzeta to occur. We will compare levels of PKMzeta after recall of memories that do or do not destabilize. We will also determine if artificially increasing the amount of PKMzeta in the brain prevents destabilization. Thirdly we will test if artificially decreasing PKMzeta renders memories destabilized. We will use these results to further investigate the unique properties of strong, destabilization-resilient memories. Lastly, we will study if learning causes a specific change to the PKMzeta gene which enables it to maintain memories before, after, and even during destabilization. We expect our experiments to reveal an integral role for PKMzeta not only in maintaining memories but also throughout memory destabilization and re-stabilization.***This research will help to bridge different fields of memory together in order to understand the common processes that underpin them. In doing so, we will be able to answer fundamental questions about how the brain stores memories and how memories manage to survive in an ever-changing brain.