Norris, RHC;
Churilov, L;
Hannan, AJ;
Nithianantharajah, J;
(2019)
Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference.
Molecular Autism
, 10
, Article 42. 10.1186/s13229-019-0292-2.
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Abstract
Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3−/y and Nlgn3R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms.
| Type: | Article |
|---|---|
| Title: | Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13229-019-0292-2 |
| Publisher version: | https://doi.org/10.1186/s13229-019-0292-2 |
| Language: | English |
| Additional information: | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Autism spectrum disorder, Perseveration, Processing speed, Reaction time, Synapse |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10115295 |
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