Activation of cortical M1 muscarinic receptors and related intracellular signaling is necessary for reactivation-induced object memory updating

Sci Rep. 2020 Jun 8;10(1):9209. doi: 10.1038/s41598-020-65836-x.

Abstract

Reactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). We have previously implicated cholinergic transmission in object memory destabilization. Here we present a novel rodent paradigm developed to assess the role of this cholinergic mechanism in qualitative object memory updating. The post-reactivation object memory modification (PROMM) task exposes rats to contextual information following object memory reactivation. Subsequent object exploratory performance suggests that the contextual information is integrated with the original memory in a reactivation- and time-dependent manner. This effect is blocked by interference with M1 muscarinic receptors and several downstream signals in perirhinal cortex. These findings therefore demonstrate a hitherto unacknowledged cognitive function for acetylcholine with important implications for understanding the dynamic nature of long-term memory storage in the normal and aging brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Lactones / pharmacology
  • Male
  • Memory* / drug effects
  • Perirhinal Cortex / metabolism
  • Perirhinal Cortex / surgery
  • Pirenzepine / pharmacology
  • Proteasome Inhibitors / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptor, Muscarinic M1 / agonists
  • Receptor, Muscarinic M1 / antagonists & inhibitors
  • Receptor, Muscarinic M1 / metabolism*
  • Scopolamine / pharmacology
  • Sulfonamides / pharmacology

Substances

  • Benzylamines
  • Inositol 1,4,5-Trisphosphate Receptors
  • Lactones
  • Proteasome Inhibitors
  • Receptor, Muscarinic M1
  • Sulfonamides
  • KN 93
  • Pirenzepine
  • Scopolamine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2