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Our research focuses on understanding the role of thyroid hormones (T4 or thyroxine and T3 or 3,5,3'-triiodothyronine) action in the central nervous system (CNS), both during development and at adult stages. We are especially interested in the identification of structural and/or functional alterations in the CNS, due to defects in thyroid hormone availability and/or signaling. To achieve this goal, we analyze the phenotype of experimental animals deficient in proteins involved in the metabolism and plasma-membrane transport of thyroid hormones using different experimental approaches. We perform in vivo studies to characterize the structural and functional consequences of alterations in the availability of thyroid hormones in the CNS. We also analyze the histopathology of human autopsy brain tissues from Allan-Herndon-Dudley syndrome patients. This syndrome is due to mutations in the monocarboxylate transporter 8 (MCT8; SLC16A2), an important thyroid hormone transporter in the brain. Our studies will shed light on the pathophysiology and on the CNS disease mechanisms associated to defects in thyroid hormone signaling and will even contribute to the development of new therapeutic strategies. These studies will also help to better understand the role of thyroid hormones in brain activity and plasticity.