Experience-dependent MeCP2 expression in the excitatory cells of mouse visual thalamus

Abstract

Loss or gain of copy number of the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2) leads to neurodevelopmental disorders (Rett and MeCP2 duplication syndrome), indicating that precisely regulated MeCP2 expression during development is critical for mental health. Consistent with this idea, MeCP2 null mutants exhibit synaptic regression in the dorsal lateral geniculate nucleus (dLGN), the visual relay center in the thalamus, a phenotype resembling that of animals reared in the dark during the visual sensitive period. It remains unclear how MeCP2 expression is regulated during circuit formation and maturation, especially in excitatory and inhibitory populations of neurons. We found that, concomitant with the initiation of the dark-rearing sensitive period, MeCP2 protein levels were elevated in glutamatergic but not GABAergic neurons of the dLGN. Moreover, MeCP2 expression in glutamatergic populations was selectively reduced by dark-rearing. Therefore, we propose that visual experience–dependent MeCP2 induction in glutamatergic populations is essential for synaptic maturation within the dLGN.