Mice Choose Sex Over Food, Even When Hungry

Researchers have discovered that hungry mice choose interaction with members of the opposite sex over eating and drinking when specific brain receptors sensitive to leptin are stimulated. The study is published in Cell Metabolism.

To mate, or to eat?

Food or sex – if you had to choose, which one would it be? It’s a “desert island icebreaker”-type question commonly put forward in conversations with friends. But how do small mammals, such as mice, approach this dilemma?

“We can only pursue one behavior at a time, so our brain has to somehow compute what will be the most rewarding behavior, or what is our most urgent need,” says Dr. Tatiana Korotkova, a neuroscientist at the University Clinic Cologne in Germany.

Innate behaviors – which are, in essence, hardwired within an organism – include eating, drinking, socializing and mating. To understand the hierarchy of these behaviors in mice, Korotkova and team studied neurons within the lateral hypothalamus (LH), a brain region commonly known as the “feeding center” due to its associations with appetite and thirst.

The researchers combined imaging, optogenetics and chemogenetics to explore the activity of LH neurons expressing leptin receptors (LepR^LH) – leptin is an appetite-suppressing hormone – and neurons that produce the hormone neurotensin (Nts^LH).

“LepR^LH neurons enhance food-rewarded behaviors and affect food intake depending on the state of the animal as well as the availability and palatability of food, indicating that the contribution of the LepR^LH population to the pursuit of nutritional rewards changes with state and opportunity,” the researchers write. In animals, activation of Nts^LH neurons consistently encourages the pursuit of water, regardless of how much water the animal has consumed.

Hungry mice prioritize social interaction with opposite sex over food

To explore how mice’s innate behaviors were influenced by hunger levels, Korotkova and colleagues compared the behavior of mice that had unlimited access to food (sated mice) to those that had been restricted from eating overnight (acutely hungry), and mice whose food consumption had been restricted for five days (chronically hungry).

“We investigated whether LepR^LH and Nts^LH populations are capable of encoding nutritional as well as non-nutritional stimuli such as conspecifics, and whether they integrate the need for social contact, food, and water with hunger or thirst to determine the hierarchy between these competing needs,” the authors write in the paper.

Incredibly small microscopes were attached to the mice’s heads to visualize activity within individual neurons as all mice explored their enclosures and engaged in social behaviors. They found that LepR^LH neurons were inhibited as the mice ate. When mice interacted with the opposite sex – i.e., potential mating partners – the same neurons were activated. When mice interacted with the same sex, however, the neurons were not activated.

Next, using light and chemical signals, Korotkova and colleagues stimulated the individual neurons to explore whether this caused any changes to the mice’s behavior.

Interestingly, stimulation of LepR^LH neurons had very little effect on sated mice, but those that were acutely hungry spent more time socializing with potential mates and were slower to approach food. In chronically hungry mice, however, stimulation of LepR^LH neurons did not affect the animals’ appetite.   

“We have this system which can only regulate moderate hunger, but not strong hunger,” says Korotkova. “This circuit might contribute to why diets don’t work: it’s not a problem to reduce your food intake for a short time, but it doesn't work if you try to do it for longer.”

Conversely, Nts^LH neuronal stimulation produced an increase in drinking behavior at the expense of socializing, both with mice of the opposite sex and those of the same sex. “We usually think about neurons having a particular function, but we found that one cell can actually encode multiple different stimuli,” says Korotkova. This makes a lot of sense biologically because behaviors need to be coordinated, and it’s much more efficient to coordinate behaviors with the same cell than by many different cell types somehow communicating with each other.”

The researchers suggest that future studies combining imaging and gene expression profiling – using spatial transcriptomics approaches – could aid our understanding of the behavior-dependent activity of individual neurons within the LH. This, they say, could “allow the targeting of functioning subgroups for selective modulation of their activity,” knowledge which may help in the treatment of obesity.

Reference: Petzold A, van den Munkhof HE, Figge-Schlensok R, Korotkova T. Complementary lateral hypothalamic populations resist hunger pressure to balance nutritional and social needs. Cell Metabolism. doi:10.1016/j.cmet.2023.02.008.

This article is a rework of a press release issued by the University Clinic Cologne in Germany. Material has been edited for length and content.