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ERIC Number: EJ1117394
Record Type: Journal
Publication Date: 2016-Nov
Pages: 8
Abstractor: As Provided
ISBN: N/A
ISSN: ISSN-1072-0502
Muscarinic Acetylcholine Receptors Act in Synergy to Facilitate Learning and Memory
Leaderbrand, Katherine; Chen, Helen J.; Corcoran, Kevin A.; Guedea, Anita L.; Jovasevic, Vladimir; Wess, Jurgen; Radulovic, Jelena
Learning & Memory, v23 n11 p631-638 Nov 2016
Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on which mAChR subtypes are critical for memory processing. Using pharmacological and genetic approaches, we found that (1) encoding and retrieval of contextual memory requires mAChR in the dorsal hippocampus (DH) and retrosplenial cortex (RSC), (2) memory formation requires hippocampal M3 and cooperative activity of RSC M[subscript 1] and M[subscript 3], and (3) memory retrieval is more impaired by inactivation of multiple M[subscript 1]-M[subscript 4] mAChR in DH or RSC than inactivation of individual receptor subtypes. Contrary to the view that acetylcholine supports learning but is detrimental to memory retrieval, we found that coactivation of multiple mAChR is required for retrieval of both recently and remotely acquired context memories. Manipulations with higher receptor specificity were generally less potent than manipulations targeting multiple receptor subtypes, suggesting that mAChR act in synergy to regulate memory processes. These findings provide unique insight into the development of therapies for amnestic symptoms, suggesting that broadly acting, rather than receptor-specific, mAchR agonists and positive allosteric modulators may be the most effective therapeutic approach.
Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://learnmem.cshlp.org
Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A