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Absence of familiarity triggers hallmarks of autism in mouse model through aberrant tail-of-striatum and prelimbic cortex signaling

Krüttner, Sebastian and Falasconi, Antonio and Valbuena, Sergio and Galimberti, Ivan and Bouwmeester, Tewis and Arber, Silvia and Caroni, Pico. (2022) Absence of familiarity triggers hallmarks of autism in mouse model through aberrant tail-of-striatum and prelimbic cortex signaling. Neuron, 110 (9). pp. 1468-1482.e5.

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Official URL: https://edoc.unibas.ch/89470/

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Abstract

Autism spectrum disorder (ASD) involves genetic and environmental components. The underlying circuit mechanisms are unclear, but behaviorally, aversion toward unfamiliarity, a hallmark of autism, might be involved. Here, we show that in Shank3; ΔC/ΔC; ASD model mice, exposure to novel environments lacking familiar features produces long-lasting failure to engage and repetitive behaviors upon re-exposure. Inclusion of familiar features at first context exposure prevented enhanced dopamine transients in tail of striatum (TS) and restored context-specific control of engagement to wild-type levels in Shank3; ΔC/ΔC; mice. Engagement upon context re-exposure depended on the activity in prelimbic cortex (PreL)-to-TS projection neurons in wild-type mice and was restored in Shank3; ΔC/ΔC; mice by the chemogenetic activation of PreL→TS projection neurons. Environmental enrichment prevented ASD-like phenotypes by obviating the dependence on PreL→TS activity. Therefore, novel context experience has a key role in triggering ASD-like phenotypes in genetically predisposed mice, and behavioral therapies involving familiarity and enrichment might prevent the emergence of ASD phenotypes.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Arber, Silvia and Falasconi, Antonio
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0896-6273
e-ISSN:1097-4199
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
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Last Modified:16 Aug 2022 08:39
Deposited On:16 Aug 2022 08:39

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