| First Author | Krüttner S | Year | 2022 |
| Journal | Neuron | Volume | 110 |
| Issue | 9 | Pages | 1468-1482.e5 |
| PubMed ID | 35219402 | Mgi Jnum | J:325075 |
| Mgi Id | MGI:7282341 | Doi | 10.1016/j.neuron.2022.02.001 |
| Citation | Kruttner S, et al. (2022) Absence of familiarity triggers hallmarks of autism in mouse model through aberrant tail-of-striatum and prelimbic cortex signaling. Neuron 110(9):1468-1482.e5 |
| abstractText | 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(DeltaC/DeltaC) 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(DeltaC/DeltaC) 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(DeltaC/DeltaC) 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. |
