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M4 muscarinic acetylcholine receptor modulation of associative learning and behavioral flexibility in a novel touchscreen cognitive assessment (845.8)
Author(s) -
Dencker Ditte,
Gould Robert,
Bubser Michael,
Bridges Thomas,
Wood Michael,
Duggan Mark,
Wood Michael,
FinkJensen Anders,
Wess Jürgen,
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.845.8
Subject(s) - touchscreen , muscarinic acetylcholine receptor , neuroscience , allosteric modulator , cognitive flexibility , associative learning , acetylcholine , cognition , psychology , flexibility (engineering) , schizophrenia (object oriented programming) , antagonist , allosteric regulation , receptor , pharmacology , medicine , computer science , mathematics , psychiatry , statistics , operating system
Recent findings indicate that selective activation of the M4 muscarinic acetylcholine receptor (M4 mAChR) may represent a novel treatment approach for the psychotic symptoms and cognitive disturbances observed in several neuropsychiatric disorders. In the present studies, cognitive performance of M4 mAChR knock‐out mice (M4‐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. While M4‐KO mice acquired the initial discrimination task in a similar number of sessions as wildtype mice, the M4‐KO mice showed impaired acquisition on all subsequent visual discriminations. In addition, the novel M4 positive allosteric modulator VU0467154 reversed disruptions in pairwise discrimination induced by MK‐801, an antagonist of the N‐methyl‐D‐aspartate subtype of glutamate receptors. These data reveal that selective M4 mAChR activation is critical for modulation of normal associative learning and behavioral flexibility in visual discrimination tasks. Moreover, our studies suggest that selective M4 PAMs may have therapeutic potential for the treatment of cognitive deficits observed in patients with schizophrenia. Grant Funding Source : This work was funded by grants# 2R01 MH73676‐06, 1R01 MH086601‐04, AstraZeneca.