Thyroid hormones maintain parvalbumin neuron functions in mouse neocortex

Parvalbumin-expressing (PV) GABAergic interneurons play a key role in maintaining the excitation-inhibition balance in the mammalian neocortex. Here we address the function of thyroid hormones in PV neurons in the mouse neocortex. To this end, Cre/loxP recombination system was used to express a dominant negative mutated receptor of thyroid hormones only in PV neurons. We analyzed the neocortical phenotype of these mice, in which thyroid hormone signaling is eliminated specifically in PV neurons, by combining genomics, histology, electrophysiology, and behavioral analysis. We found significantly altered gene expression, reduced expression of key perineuronal net components, reduced PV neuron excitability, behavioral hyperactivity and increased susceptibility to seizures. These results highlight that thyroid hormones are not only required for the differentiation of PV interneurons, but also for the maintenance of their inhibitory function after the onset of parvalbumin expression.