LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants.

ABSTRACT:

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.

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,

SUBMITTER: Fazel Darbandi S 

PROVIDER: S-EPMC8903688 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature