Date of Award
Doctor of Philosophy
Fred J. Helmstetter
Fred J. Helmstetter, Devin Mueller, Karyn M. Frick, Ava J. Udvadia, James R. Moyer
Amygdala, CaMKII, Fear Conditioning, Memory, Proteasome, Reconsolidation
Reconsolidation is thought to be a process whereby consolidated memories can be modified following retrieval. However, very little is known about the molecular mechanisms that regulate this reconsolidation process. In the present series of experiments we tested if memories "destabilize" or become labile following retrieval through a specific signaling pathway. We found that retrieval of a contextual fear memory differentially increased proteasome activity in the amygdala and hippocampus and resulted in unique changes in AMPA receptor subunit expression in these brain regions. These changes were dependent on CaMKII activity, which was required for increases in Rpt6-S120 phosphorylation, proteasome activity and GluR2/3 in the amygdala and hippocampus. Interestingly, CaMKII-mediated protein degradation in the amygdala was critical for changes in proteasome activity and AMPA receptor subunit expression in the hippocampus, suggesting that protein degradation in the amygdala is critical for the reconsolidation of a contextual fear memory in the hippocampus. Additionally, we found that auditory fear memories destabilize in the amygdala but reconsolidate in both the amygdala and hippocampus following retrieval, suggesting that the amygdala and hippocampus may interact to reconsolidate memories that are normally hippocampus-independent. Finally, we found that contextual information, but not prediction error, was the new information present at retrieval that controlled the destabilization and reconsolidation of a retrieved auditory fear memory. Collectively, these results suggest that fear memories undergo systems reconsolidation following retrieval where they destabilize through a specific cellular pathway mediated by CaMKII in the amygdala, and that contextual information may be the new information present at retrieval that controls the reconsolidation-dependent updating of fear memories in the amygdala.
Jarome, Timothy, "The Role of a CaMKII/PKA-Protein Degradation-GluR2 Pathway in the Control of Memory Updating Following Retrieval" (2013). Theses and Dissertations. 232.