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: | Alexa E. Horner, Robbie McLaren-Jones, Jess Nithianantharajah, Rebecca H. C. Norris, Maksym V. Kopanitsa, Liam Alexander, Seth G. N. Grant, Noboru H. Komiyama |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Scaffold protein Computational biology SYNGAP1 Biology Associative learning SHANK2 03 medical and health sciences Behavioral Neuroscience 030104 developmental biology 0302 clinical medicine Neurology Neurotransmitter receptor Postsynaptic potential Synaptic plasticity Genetics Postsynaptic density 030217 neurology & neurosurgery |
| Zdroj: | Genes, Brain and Behavior. 20 |
| ISSN: | 1601-183X 1601-1848 |
| DOI: | 10.1111/gbb.12723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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