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Title: Touchscreen testing reveals clinically relevant cognitive abnormalities in a mouse model of schizophrenia lacking metabotropic glutamate receptor 5.
Austin Authors: Zeleznikow-Johnston, Ariel M;Renoir, Thibault;Churilov, Leonid ;Li, Shanshan;Burrows, Emma L;Hannan, Anthony J
Affiliation: The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia
Issue Date: 6-Nov-2018
Date: 2018-11-06
Publication information: Scientific Reports 2018; 8(1): 16412
Abstract: Metabotropic glutamate receptor 5 (mGlu5) has been implicated in certain forms of synaptic plasticity and cognitive function. mGlu5 knockout (KO) mice and mGlu5 antagonists have been previously used to study the pathophysiology of schizophrenia as they have been shown respectively to display or induce endophenotypes relevant to schizophrenia. While schizophrenia presents with generalized cognitive impairments, the cognitive phenotype of mice lacking mGlu5 has so far only been explored using largely hippocampal-dependent spatial and contextual memory tasks. To address this, we used a touchscreen system to assess mGlu5 KO mice for pairwise visual discrimination, reversal learning, and extinction of an instrumental response requiring no discrimination. Furthermore, we tested the role of mGlu5 in working memory using the Trial-Unique Non-Matching to Location (TUNL) task utilizing pharmacological ablation. mGlu5 KO mice were impaired on discrimination learning, taking longer to reach criterion and requiring more correction learning trials. Performance on reversal learning was also impaired, with mGlu5 KO mice demonstrating a perseverative phenotype. The mGlu5 KO mice responded at a higher rate during extinction, consistent with this perseverative profile. In contrast, wildtype mice treated acutely with an mGlu5 antagonist (MTEP) showed no deficits in a touchscreen task assessing working memory. The present study demonstrates learning and memory deficits as well as an increased perseverative phenotype following constitutive loss of mGlu5 in this mouse model of schizophrenia. These findings will inform translational approaches using this preclinical model and the pursuit of mGlu5 as therapeutic target for schizophrenia and other brain disorders.
DOI: 10.1038/s41598-018-33929-3
ORCID: 0000-0002-9807-6606
Journal: Scientific Reports
PubMed URL: 30401923
Type: Journal Article
Appears in Collections:Journal articles

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