A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus.

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Publication Year:
2023
Authors:
Predrag Jovanovic, Allan-Hermann Pool, Nancy Morones, Yidan Wang, Edward Novinbakht, Nareg Keshishian, Kaitlyn Jang, Yuki Oka, Celine E Riera
PubMed ID:
37582805
Funding Grants:
Public Summary:
Smell is really important for animals like mice to detect predators and escape danger. When mice smell a predator, their bodies heat up by activating a special fat called brown fat, which helps them get ready to run away. This study looked at how this heating response works, especially in female mice. They found that a specific predator smell caused female mice to heat up, eat less, and release stress hormones. When they activated certain brain cells involved in smell, they saw the same heating and stress hormone release in females. They also discovered that brain areas connected to smell, especially a part called the dorsomedial hypothalamus, contain special neurons that respond to predator smells. Turning these neurons on or off affected the mice’s body heat and eating behavior during stress.
Scientific Abstract:
Olfactory cues are vital for prey animals like rodents to perceive and evade predators. Stress-induced hyperthermia, via brown adipose tissue (BAT) thermogenesis, boosts physical performance and facilitates escape. However, many aspects of this response, including thermogenic control and sex-specific effects, remain enigmatic. Our study unveils that the predator odor trimethylthiazoline (TMT) elicits BAT thermogenesis, suppresses feeding, and drives glucocorticoid release in female mice. Chemogenetic stimulation of olfactory bulb (OB) mitral cells recapitulates the thermogenic output of this response and associated stress hormone corticosterone release in female mice. Neuronal projections from OB to medial amygdala (MeA) and dorsomedial hypothalamus (DMH) exhibit female-specific cFos activity toward odors. Cell sorting and single-cell RNA-sequencing of DMH identify cholecystokinin (CCK)-expressing neurons as recipients of predator odor cues. Chemogenetic manipulation and neuronal silencing of DMH(CCK) neurons further implicate these neurons in the propagation of predator odor-associated thermogenesis and food intake suppression, highlighting their role in female stress-induced hyperthermia.