Thyroid hormones maintain parvalbumin neuron functions in the mouse neocortex

Parvalbumin-expressing GABAergic interneurons are crucial for maintaining excitation/inhibition balance in the neocortex. The postnatal maturation of parvalbumin neurons is highly sensitive to thyroid hormone deficiency. The present study addressed the role of thyroid hormones in mature parvalbumin neurons. Using genetically modified mouse models, we selectively disrupted thyroid hormone signaling in parvalbumin neurons after the onset of parvalbumin expression. Genomic, histological, electrophysiological, sleep, and behavioral analyses were conducted. Mutant mice showed reduced expression of perineuronal net components, decreased neuron excitability, altered gamma oscillations, behavioral hyperactivity, increased wakefulness, delayed sleep onset, and greater susceptibility to seizures. These results demonstrate that thyroid hormones are essential not only for the maturation but also for the maintenance of cortical parvalbumin neuron function after the onset of parvalbumin expression. Disruption of thyroid hormone signaling, during development or adulthood, may thus contribute to neurological and psychiatric disorders involving impaired cortical oscillations.