We previously linked TSHZ3 haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatal Tshz3deletion in mice results in behavioral traits relevant to the two core domains of ASD: social interaction deficits and repetitive behaviors.

Here we show that Tshz3 deletion in cortical projection neurons (CPNs) or in striatal cholinergic interneurons (SCINs) does not affect their numbers, but alters their electrophysiological features and the synaptic properties of the corticostriatal circuitry. Moreover, Tshz3loss in CPNs results in social interaction deficits, while its deletion in SCINs results in repetitive patterns of behavior, thus segregating distinct ASD behavioral traits.

These findings provide novel insights into the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.



To know more

Caubit, X., Gubellini, P., Roubertoux, P.L. et al. Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors. Transl Psychiatry 12, 106 (2022). https://doi.org/10.1038/s41398-022-01865-6


Lydia Kerkerian-Le Goff ; Laurent Fasano