Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2.

Autor: Horner AE; Synome Ltd, Babraham Research Campus, Cambridge, UK., Norris RH; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia., McLaren-Jones R; Synome Ltd, Babraham Research Campus, Cambridge, UK., Alexander L; Synome Ltd, Babraham Research Campus, Cambridge, UK., Komiyama NH; Genes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain (SIDB), Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK., Grant SGN; Genes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain (SIDB), Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK., Nithianantharajah J; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia., Kopanitsa MV; Synome Ltd, Babraham Research Campus, Cambridge, UK.; UK Dementia Research Institute and Department of Brain Sciences, Imperial College, London, UK.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2021 Jan; Vol. 20 (1), pp. e12723. Date of Electronic Publication: 2020 Dec 29.
DOI: 10.1111/gbb.12723
Abstrakt: The postsynaptic terminal of vertebrate excitatory synapses contains a highly conserved multiprotein complex that comprises neurotransmitter receptors, cell-adhesion molecules, scaffold proteins and enzymes, which are essential for brain signalling and plasticity underlying behaviour. Increasingly, mutations in genes that encode postsynaptic proteins belonging to the PSD-95 protein complex, continue to be identified in neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability and epilepsy. These disorders are highly heterogeneous, sharing genetic aetiology and comorbid cognitive and behavioural symptoms. Here, by using genetically engineered mice and innovative touchscreen-based cognitive testing, we sought to investigate whether loss-of-function mutations in genes encoding key interactors of the PSD-95 protein complex display shared phenotypes in associative learning, updating of learned associations and reaction times. Our genetic dissection of mice with loss-of-function mutations in Syngap1, Nlgn3, Dlgap1, Dlgap2 and Shank2 showed that distinct components of the PSD-95 protein complex differentially regulate learning, cognitive flexibility and reaction times in cognitive processing. These data provide insights for understanding how human mutations in these genes lead to the manifestation of diverse and complex phenotypes in NDDs.
(© 2020 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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