Thyroid hormones act as a timer for the postnatal maturation of parvalbumin neurons in mouse neocortex [RUN125]

A finely tuned balance between excitation and inhibition is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders. Understanding GABAergic neuron maturation processes is thus currently a major challenge in basic neuroscience. Thyroid hormones (THs) are required for proper maturation of parvalbumin-expressing GABAergic interneurons in the mouse neocortex. However, the timeline of this TH action has yet to be elucidated. Here, we used several mouse models expressing dominant negative mutations of the TH nuclear receptor α1 (TRα1), to better define the time window during which THs promote the postnatal maturation of parvalbumin neurons. Histological observations revealed that the action of TH during the first three postnatal weeks was necessary to initiate the expression of parvalbumin and the elaboration of a specialized extracellular matrix called the perineuronal net. By contrast, after the third postnatal week, TH action on parvalbumin neuron maturation appeared to be somewhat dispensable. Transcriptome analysis of neocortical GABAergic neurons two weeks after birth identified a small set of putative target genes for TRα1. These genes are at the origin of the postnatal remodeling of the repertoire of ions channels and the elaboration of perineuronal nets. These data suggest that THs act as a timer to define the temporal boundaries of the critical period of heightened cortical plasticity, which plays a fundamental role in the development of neuronal circuits.