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Linking muscarinic receptor activation to UPS-mediated object memory destabilization: Implications for long-term
Mikaela L Stiver1, Jacob M Cloke1, Natalie Nightingale1
1Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
Neurobiology of Learning and Memory
|October 15, 2017
Summary
Novelty destabilizes consolidated memories via M1 muscarinic acetylcholine receptors (mAChRs) and the ubiquitin proteasome system (UPS). This pathway, involving calcium release, is crucial for memory updating and reconsolidation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cognitive Science
Background:
- Consolidated memories can be destabilized during reactivation, facilitating updating.
- Cholinergic muscarinic receptor (mAChR) activation can destabilize object memories.
- Synaptic protein degradation via the ubiquitin proteasome system (UPS) is linked to memory destabilization.
Purpose of the Study:
- To investigate the intracellular pathway linking M1 mAChRs, calcium release, and UPS activity in object memory destabilization.
- To determine if M1 mAChRs are necessary for novelty-induced memory destabilization.
- To explore the role of inositol triphosphate receptors (IP3Rs) in this process.
Main Methods:
- Utilized a modified spontaneous object recognition task in rats.
- Administered microinfusions into the perirhinal cortex (PRh).
- Tested the effects of proteasome inhibition and IP3R antagonism.
Main Results:
- M1 mAChRs are essential for destabilizing object memories in response to novelty.
- Inhibition of the proteasome or IP3Rs in the PRh blocked memory destabilization induced by novelty or M1 mAChR stimulation.
- Established a link between M1 receptors, IP3Rs, calcium release, and UPS activity.
Conclusions:
- Cholinergic signaling, specifically via M1 mAChRs, plays a critical role in object memory destabilization through a pathway involving IP3Rs, calcium release, and the UPS.
- This pathway is fundamental for memory updating and long-term storage modification.
- Highlights a novel mechanism for cholinergic involvement in memory plasticity.