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Parabrachial Foxp2-expressing neurons are necessary for sustaining core body temperature in the cold
Journal article   Open access   Peer reviewed

Parabrachial Foxp2-expressing neurons are necessary for sustaining core body temperature in the cold

Fillan S. Grady, Shantelle A. Graff, McKenna M. Warnock, Silvia Gasparini, Margaret M. Tish, Yuxi Li, Gordon F. Buchanan, Jon M. Resch and Joel C. Geerling
iScience, Vol.28(8), 112764
08/2025
DOI: 10.1016/j.isci.2025.112764
PMCID: PMC12283563
PMID: 40703448
url
https://doi.org/10.1016/j.isci.2025.112764View
Published (Version of record) Open Access

Abstract

Cold environmental temperature is a threat to survival. Sustaining core body temperature in the cold requires a dynamic set of adaptive responses known as “cold defense,” but the neural circuitry orchestrating these responses remains unclear. We identified a cluster of Atoh1-derived, Foxp2-expressing glutamatergic neurons in the lateral parabrachial nucleus (PB) that are activated by exposing mice to cold environmental temperature. Eliminating Foxp2-expressing PB neurons caused body temperature to plummet in the cold. Mice lacking these neurons had normal wakefulness, movement and appetite at room temperature, and their autonomic cold-defense responses remained intact. However, these mice had reduced metabolism and locomotor activity in the cold, and thermal discrimination was impaired. Our results indicate that thermosensory information relayed through Foxp2-expressing PB neurons is essential for sensing and surviving a cold environment. [Display omitted] •Cold exposure activates neurons in the parabrachial nucleus that express Foxp2.•Deleting Foxp2 neurons from the parabrachial nucleus drops body temperature in the cold.•At room temperature, mice without these neurons have normal activity and appetite.•Mice lacking these neurons have impaired thermal preference and metabolism in the cold. Grady et al. investigated a cluster of neurons in the brainstem that are activated during exposure to cold. Deleting these neurons dramatically lowered body temperature in cold conditions, impacting metabolism, movement, and thermal perception without affecting baseline activity or appetite.
Thermoregulation appetite cold defense homeostasis parabrachial complex parabrachial nucleus wakefulness

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