Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation

Abstract

Please cite this article as: Blake, M.G., Boccia, M.M., Krawczyk, M.C., Delorenzi, A., Baratti, C.M., Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation, Neurobiology of Learning and Memory (2012), doi: http://dx.doi. org/10.1016/j.nlm.2012.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia. Research highlights-Pre-training administration of scopolamine leads to memory impairment.-Intra-hippocampal administration of choline modulates memory reconsolidation -Choline reverses scopolamine-induced amnesia by enhancing memory reconsolidation -Low doses of scopolamine cause memory expression deficit, but not storage impairment -Reconsolidation could modify the ability of a memory for being expressed later

Dissociation between memory reactivation and its behavioral expression: Scopolamine interferes with memory expression without disrupting long-term storage

“…Results strongly suggest that the neural representation of a VDS-context association persists after the scopolamine administration, since this representation can be specifically reactivated by a reminder and can enter a new labile phase. Remarkably, these results are in line with studies that show a dissociation between the mechanisms mediating memory labilization and the mechanisms that underlie the behavioral expression of memory (Ben et al, 2006;Coccoz et al, 2011;Frenkel et al, 2010;Sevenster et al, 2012;Blake, Boccia, Krawczyk, Delorenzi & Baratti, 2012).…”

“…However, these memories would be in fact retrieved, labilized and enhanced during the reconsolidation process, allowing them to be expressed long term, i.e.,. to take control of behavior in subsequent evaluations (Blake et al, 2012). Thus, memory impairment observed in the scopolamine-induced experimental amnesia, and conceivably in Alzheimer's disease patients, caused by cholinergic dysfunction, might actually be a symptom of expression impairment rather than memory loss.…”

Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation

“…Our previous studies highlighted that retrieval and memory expression are not interchangeable concepts. Hence, memory expression during the reminder session is not a prerequisite to trigger reconsolidation since unexpressed memories can be reactivated and reconsolidated (Barreiro, Suarez, Lynch, Molina, and Delorenzi, 2013;Blake, Boccia, Krawczyk, Delorenzi, and Baratti, 2012;Caffaro, Suarez, Blake, and Delorenzi, 2012;Coccoz, Maldonado, and Delorenzi, 2011;Frenkel, Maldonado, and Delorenzi, 2005;Frenkel, Suarez, Maldonado, and Delorenzi, 2010;Maza, Locatelli, and Delorenzi, 2016a). For instance, we showed in crabs that the retrieval deficit induced by a pharmacological manipulation (administration of glutamate receptor antagonists) interferes with memory expression (Barreiro et al, 2013;Delorenzi, Maza, Suarez, Barreiro, Molina, and Stehberg, 2014).…”

“…Regardless of poor memory expression at the time of memory reactivation due to forgetting (1 or 3 weeks after training), robust memory expression can be found at testing sessions if stress (1 st week) or glucose administration (3 th week) are concurrent with the reconsolidation phase. Thus, the behavioral expression of consolidated memories is not required for memory reactivation and reconsolidation (Barreiro et al, 2013;Ben Mamou et al, 2006;Blake et al, 2012;Delorenzi et al, 2014;Frenkel et al, 2005;Milton et al, 2013;Rodriguez-Ortiz et al, 2012;Santoyo-Zedillo et al, 2014a;Sevenster et al, 2012).…”

Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

“…Lesions in mice resulted in deficits in working spatial memory in the T-maze [64] and poor utilisation of spatial cues in the Morris water maze [65][66][67] and Barnes maze [66], as well as impaired cue-independent (egocentric) navigation [68]. These lesion studies were complemented by pharmacological approaches in which cholinergic transmission was blocked with the muscarinic receptor antagonist scopolamine, which resulted in similar cognitive changes [69][70][71][72][73].…”