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Influence of M 1 muscarinic acetylcholine receptor activation on arousal and cognitive performance using electroencephalography and novel touchscreen cognition assessment (845.5)
Author(s) -
Gould Robert,
Nedelcovych Michael,
Dencker Ditte,
Melancon Bruce,
Stauffer Shaun,
Wood Michael,
Wess Jurgen,
Xiang Zixiu,
Lindsley Craig,
Conn P,
Jones Carrie
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.845.5
Subject(s) - cognition , muscarinic acetylcholine receptor , neuroscience , touchscreen , psychology , arousal , effects of sleep deprivation on cognitive performance , electroencephalography , cholinergic , schizophrenia (object oriented programming) , medicine , receptor , psychiatry , operating system , computer science
Cognitive impairments associated with neuropsychiatric disorders such as Alzheimer’s Disease and schizophrenia remain largely untreated. Cholinergic hypofunction has been hypothesized to contribute to cognitive deficits yet the role of subtype‐selective muscarinic acetylcholine receptors (mAChR) remains unclear. Electroencephalography (EEG) studies demonstrated that the M 1 mAChR partial agonist VU0357017 and positive allosteric modulator (PAM) BQCA induced wake‐promoting effects and a shift from low to high frequency power during wake suggesting enhanced arousal and a pro‐cognitive signature. Cognitive performance of M 1 mAChR knockout (M 1 KO) mice was examined across a series of computer touchscreen‐based pairwise discrimination tasks assessing susceptibility to interference from previously learned competing sets of information, a cognitive deficit present in neuropsychiatric disorders. M 1 KO and wildtype mice acquired the initial discrimination at similar rates yet M 1 KO mice showed impaired acquisition of subsequent discriminations. The current data demonstrate M 1 mAChR mediation of susceptibility to interference following repeated learning, supporting development of M 1 mAChR subtype‐selective compounds as pharmacotherapies for cognitive impairments associated with neuropsychiatric disorders. Grant Funding Source : Supported By MH086601, MH087965, MH093366, NS065867