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Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses

 Jisoo Lim  ;  Eosu Kim  ;  Hyun Jong Noh  ;  Shinwon Kang  ;  Benjamin U. Phillips  ;  Dong Goo Kim  ;  Timothy J. Bussey  ;  Lisa Saksida  ;  Christopher J. Heath  ;  Chul Hoon Kim 
 Molecular Brain, Vol.12(1) : e37, 2019 
Journal Title
 Molecular Brain 
Issue Date
Animals ; Behavior, Animal* ; Choice Behavior ; Decision Making ; Discrimination (Psychology) ; Extinction, Psychological ; Feeding Behavior ; Gene Deletion ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, Metabotropic Glutamate 5/antagonists & inhibitors ; Receptor, Metabotropic Glutamate 5/deficiency* ; Receptor, Metabotropic Glutamate 5/metabolism ; Stress, Psychological/pathology* ; Task Performance and Analysis ; Visual Perception
Behavioural flexibility ; Extinction ; Perseveration ; Progressive ratio schedule ; Reversal learning ; mGluR5
Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress.Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs.Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
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