Shank3a/b isoforms regulate the susceptibility to seizures and thalamocortical development in the early postnatal period of mice.

Epileptic seizures are distinct but frequent comorbidities in children with autism spectrum disorder (ASD). The hyperexcitability of cortical and subcortical neurons appears to be involved in both phenotypes. However, little information is available concerning which genes are involved and how they regulate the excitability of the thalamocortical network. In this study, we investigate whether an ASD-associated gene, SH3 and multiple ankyrin repeat domains 3 (Shank3), plays a unique role in the postnatal development of thalamocortical neurons. We herein report that Shank3a/b, the splicing isoforms of mouse Shank3, were uniquely expressed in the thalamic nuclei, peaking from two to four weeks after birth. Shank3a/b-knockout mice showed lower parvalbumin signals in the thalamic nuclei. Consistently, Shank3a/b-knockout mice were more susceptible to generalized seizures than wild-type mice after kainic acid treatments. Together, these data indicate that NT-Ank domain of Shank3a/b regulates molecular pathways that protect thalamocortical neurons from hyperexcitability during the early postnatal period of mice.