Hochbaum, Daniel RHulshof, LaurenUrke, AmandaWang, WengangDubinsky, Alexandra CFarnsworth, Hannah CHakim, RichardLin, SherryKleinberg, GionaRobertson, KeiramariePark, CanariaSolberg, AlyssaYang, YechanBaynard, CarolineNadaf, Naeem MBeron, Celia CGirasole, Allison EChantranupong, LynneCortopassi, Marissa DProuty, ShannonGeistlinger, LudwigBanks, Alexander SScanlan, Thomas SDatta, Sandeep RobertGreenberg, Michael EBoulting, Gabriella LMacosko, Evan ZSabatini, Bernardo L2024-09-252024-09-252024-08-19Hochbaum DR, Hulshof L, Urke A, Wang W, Dubinsky AC, Farnsworth HC, Hakim R, Lin S, Kleinberg G, Robertson K, Park C, Solberg A, Yang Y, Baynard C, Nadaf NM, Beron CC, Girasole AE, Chantranupong L, Cortopassi MD, Prouty S, Geistlinger L, Banks AS, Scanlan TS, Datta SR, Greenberg ME, Boulting GL, Macosko EZ, Sabatini BL. Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration. Cell. 2024 Aug 19:S0092-8674(24)00835-3. doi: 10.1016/j.cell.2024.07.041. Epub ahead of print. PMID: 39178853.1097-417210.1016/j.cell.2024.07.04139178853https://hdl.handle.net/20.500.14038/53815Animals adapt to environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here, we find that thyroid hormone-a regulator of metabolism in many peripheral organs-directly activates cell-type-specific transcriptional programs in the frontal cortex of adult male mice. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulatory genes in both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread plasticity of cortical circuits. Indeed, whole-cell electrophysiology revealed that thyroid hormone alters excitatory and inhibitory synaptic transmission, an effect that requires thyroid hormone-induced gene regulatory programs in presynaptic neurons. Furthermore, thyroid hormone action in the frontal cortex regulates innate exploratory behaviors and causally promotes exploratory decision-making. Thus, thyroid hormone acts directly on the cerebral cortex in males to coordinate exploratory behaviors with whole-body metabolic state.en© 2024 The Author(s). Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/body-brain coordinationexplorationmetabolismneurosciencesynaptic plasticitythyroid hormonetranscriptionally regulated behaviorJournal ArticleCell