Background
Tbr1 encodes a T-box transcription factor and is considered a high confidence autism spectrum disorder (ASD) gene. Tbr1 is expressed in the postmitotic excitatory neurons of the deep neocortical layers 5 and 6. Postnatally and neonatally, Tbr1 conditional mutants (CKOs) have immature dendritic spines and reduced synaptic density. However, an understanding of Tbr1's function in the adult mouse brain remains elusive.
Conclusions
LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission.
Methods
We used conditional mutagenesis to interrogate Tbr1's function in cortical layers 5 and 6 of the adult mouse cortex.
Results
Adult Tbr1 CKO mutants have dendritic spine and synaptic deficits as well as reduced frequency of mEPSCs and mIPSCs. LiCl, a WNT signaling agonist, robustly rescues the dendritic spine maturation, synaptic defects, and excitatory and inhibitory synaptic transmission deficits. Conclusions: LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission.