RT Journal Article SR Electronic T1 A novel role for cortical acetylcholine in object memory updating JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.08.940064 DO 10.1101/2020.02.08.940064 A1 Kristen H. Jardine A1 Cassidy E. Wideman A1 Chelsea MacGregor A1 Cassandra Sgarbossa A1 Dean Orr A1 Krista A. Mitchnick A1 Boyer D. Winters YR 2020 UL http://biorxiv.org/content/early/2020/02/08/2020.02.08.940064.abstract AB 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 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.