Hunger and hormones drive aggression in mice

Researchers at the Francis Crick Institute have found that hunger can make virgin female mice aggressive towards pups, but only in certain hormonal states. These mice would usually ignore other females' pups or show parent-like caring behavior.

In a study published today in Nature, the team found that the switch towards aggression only occurs at certain stages of the reproductive cycle and that hunger and hormone signals are integrated in a particular brain region to elicit this response.

In order to understand how specific bodily states shape information processing in the brain, the team investigated how virgin female mice interact with pups when sated or hungry. After just a few hours after food is removed, a substantial number of these females became aggressive towards pups, an effect that was diminished when the mice were fed.

These mice were only aggressive towards pups, and continued to act normally in other contexts, such as towards other adult mice or prey. This suggested to the research team that hunger and parenting circuits in the brain somehow interact.

Finding the control center in the brain

The researchers focused on neurons in the hypothalamus that are responsible for regulating appetite, the so-called AgRP neurons. They found that these neurons also mediated the effect of food deprivation on behavior towards pups. Artificially switching on AgRP neurons increased pup-directed aggression in satiated mice, and silencing them diminished pup-directed aggression in hungry mice.

By tracing and manipulating projections from AgRP neurons, the researchers found that a region called the medial preoptic area (MPOA), important for parental behavior, was a key downstream region for the influence of hunger on parental behavior.

Coordinating hunger and reproductive state

Interestingly, only about 60% of females showed aggression towards pups even when hunger levels were the same in all the mice. So the team set out to investigate whether reproductive state might influence aggression.

They found that mice at certain stages of the reproductive 'estrous' cycle were more likely to become aggressive towards pups. Specifically, the ratio of the ovarian hormones oestradiol and progesterone, which fluctuates across the cycle, sets the responsiveness of MPOA neurons.

The team then showed that hunger information carried by AgRP neurons dampens neuronal activity in the MPOA, stimulating the switch from caring behavior to pup-directed aggression.

The team believe that these behavioral changes during the estrous cycle reflect a change in priorities as the mouse's internal states fluctuate.

Jonny Kohl, Group Leader of the State-Dependent Neural Processing Laboratory at the Crick, said: "Our work focuses on mouse behavior, and we know that humans don't experience the same simple behavioral switches, but these findings stress the importance of understanding hormones when looking at how different physical states interact in the brain.

"Humans experience many internal states at once, and how the brain integrates these signals and how they shape behavior remains largely unknown. Work like this can begin to unravel the mechanisms underlying the integration of states, as brain architecture and hormones are very similar between species."

Female mice have to decide how to behave towards pups based on their current internal state, as parental interactions are usually very energetically costly. We've shown that their brains integrate hunger and reproductive state in the same region to elicit a state-dependent behavioral response. It would be interesting to next look at how this integrated signal brings about behavioral changes downstream of the MPOA."

Mingran Cao, former PhD student in the State-Dependent Neural Processing Laboratory at the Crick and first author of the study