Thyroid hormones act as a timer for the postnatal maturation of parvalbumin neurons in the neocortex

Abstract

Thyroid hormones (THs) are required for proper maturation of parvalbumin-expressing GABAergic interneurons in the mouse neocortex, which function is essential to maintain a proper balance between neuronal excitation and inhibition. 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 1 (TR1), to better define the time window during which THs promote the maturation of parvalbumin neurons. The action of THs during the first three postnatal weeks appears to be necessary to initiate the elaboration of a specialized extracellular matrix called the perineuronal net. Transcriptome analysis identified a small set of putative target genes for TR1, which 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. Significance statementThyroid hormones exert a major influence on late neurodevelopment, acting directly on gene expression by binding to nuclear receptors present in all cell types. This study reports the discovery of a direct link between the transcriptional regulation exerted by the thyroid hormones in GABAergic neurons and the timing of the critical period of heightened plasticity. This provides a general framework to understand the pathology associated with altered thyroid hormone signaling.