Involvement of Muscarinic Cholinergic Receptors Within the Dorsal Hippocampus in the Destabilization of Object Location Memories

Huff, Andrew
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University of Guelph

Previously consolidated memories become reactivated by exposure to cues associated with the original learning event. This can cause destabilization, rendering memories vulnerable to disruption or modification. Memories must then be re-stabilized through the protein-synthesis dependent process of reconsolidation. Our research group has previously identified an M1 muscarinic cholinergic receptor (mAChR)-dependent mechanism of object memory destabilization involving inositol 1,4,5-triphosphate receptors (IP3Rs), calcium/calmodulin-dependent protein kinase II (CaMKII), and the ubiquitin proteasome system that exists within perirhinal cortex. We hypothesized that this mechanism is generalizable to other brain regions. Accordingly, we used the object location task, which is dorsal hippocampus (dHPC)-dependent, to show that reactivation-dependent destabilization of object location memories requires M1 mAChRs, IP3Rs, CaMKII, and necessitates a protein synthesis-dependent reconsolidation process within the dHPC. This research enhances our understanding of long-term memory dynamics, and suggests implications for the treatment of disorders such as Alzheimer’s Disease and Post-traumatic stress disorder.

Memory destabilization, Muscarinic cholinergic receptor, Dorsal hippocampus, Object location memory, Reconsolidation