Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration
Animals 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.
Authors
- Sandeep Robert Datta (ORCID: https://orcid.org/0000-0002-8068-3862)
- Lauren Hulshof
- Lynne Chantranupong (ORCID: https://orcid.org/0000-0001-9814-5264)
- Canaria Park
- Alexandra C. Dubinsky
- Marissa D. Cortopassi
- Thomas S. Scanlan (ORCID: https://orcid.org/0000-0003-2612-5445)
- Ludwig Geistlinger (ORCID: https://orcid.org/0000-0002-2495-5464)
- Gabriella L. Boulting (ORCID: https://orcid.org/0000-0003-2012-1259)
- Wengang Wang (ORCID: https://orcid.org/0000-0002-8870-2634)
- Bernardo L. Sabatini (ORCID: https://orcid.org/0000-0003-0095-9177)
- Naeem Nadaf (ORCID: https://orcid.org/0000-0002-7805-8523)
- Sherry Lin (ORCID: https://orcid.org/0000-0002-1275-8391)
- Allison E. Girasole (ORCID: https://orcid.org/0000-0002-1055-9030)
- Richard Hakim (ORCID: https://orcid.org/0000-0002-6991-1801)
- Celia Beron (ORCID: https://orcid.org/0000-0003-4289-253X)
- Daniel R. Hochbaum (ORCID: https://orcid.org/0000-0001-6220-6651)
- Caroline Baynard
- Evan Z. Macosko (ORCID: https://orcid.org/0000-0002-2794-5165)
- Michael E. Greenberg (ORCID: https://orcid.org/0000-0003-1380-2160)
- Keiramarie Robertson
- Alexander S. Banks (ORCID: https://orcid.org/0000-0003-1787-6925)
- Giona Kleinberg (ORCID: https://orcid.org/0000-0002-6900-0215)
- Hannah C Farnsworth
- Amanda Urke
- Yechan Yang
- Shannon Prouty
- Alyssa Solberg
Institutions
- Broad Institute (US)
- Beth Israel Deaconess Medical Center (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Oregon Health & Science University (US)
- University of Massachusetts Chan Medical School (US)
- Center for Systems Biology (US)
Publication Details
- Journal
- Cell
- Published
- 2024-08-22
- DOI
- https://doi.org/10.1016/j.cell.2024.07.041
- Citations
- 34
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 9.12
Funders
- Howard Hughes Medical Institute
- Burroughs Wellcome Fund
- Brain and Behavior Research Foundation
- National Institutes of Health
- National Institute of General Medical Sciences