Cold memories control whole-body thermoregulatory responses

• 成果类型: Article
• 署名作者: Munoz Zamora, Andrea; Douglas, Aaron; Conway, Paul B.; Urrieta, Esteban; Moniz, Taylor; O'Leary, James D.; Marks, Lydia; Denny, Christine A.; Ortega-de San Luis, Clara; Lynch, Lydia; Ryan, Tomas J.
• 署名单位: Trinity College Dublin; Trinity College Dublin; Allen Institute for Brain Science; New York State Psychiatry Institute; Universidad de Jaen; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Princeton University; Princeton University; Florey Institute of Neuroscience & Mental Health; University of Melbourne; Canadian Institute for Advanced Research (CIFAR)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2635
• DOI: 10.1038/s41586-025-08902-6
• 发表日期: 2025-05-22
• 关键词: brown adipose-tissue; engram cells; temperature; mice; neurons; thermogenesis; hypothalamus; activation; substrate

摘要

Environmental thermal challenges trigger the brain to coordinate both autonomic and behavioural responses to maintain optimal body temperature1, 2, 3-4. It is unknown how temperature information is precisely stored and retrieved in the brain and how it is converted into a physiological response. Here we investigated whether memories could control whole-body metabolism by training mice to remember a thermal challenge. Mice were conditioned to associate a context with a specific temperature by combining thermoregulatory Pavlovian conditioning with engram-labelling technology, optogenetics and chemogenetics. We report that if mice are returned to an environment in which they previously experienced a 4 degrees C cold challenge, they increase their metabolic rates regardless of the actual environmental temperature. Furthermore, we show that mice have increased hypothalamic activity when they are exposed to the cold, and that a specific network emerges between the hippocampus and the hypothalamus during the recall of a cold memory. Both natural retrieval and artificial reactivation of cold-sensitive memory engrams in the hippocampus mimic the physiological responses that are seen during a cold challenge. These ensembles are necessary for cold-memory retrieval. These findings show that retrieval of a cold memory causes whole-body autonomic and behavioural responses that enable mice to maintain thermal homeostasis.