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Experience shapes mouse fighting and mating behaviors

Composite image of neurons active in mouse brains over three days. Day 1, red; day 2, green; day 3, blue. Neurons active all three days are white. Outlined are 20 example neurons (out of 135) that could be identified in all three days of imaging.Anderson lab, Caltech, Nature

Mice are territorial. When two male mice meet, they often attack to protect their space. When a male mouse meets a female mouse, however, they often mate. These behaviors are thought to be instinctive and thus genetically encoded, or “hard wired,” into the brain.

Many nerve cells, or neurons, work together to form neural circuits that conduct messages through the brain. Multiple levels of neural circuits are involved in interpreting and responding to an event, such as meeting a new mouse and deciding what sex it is and whether to attack it or mate with it.

Studies have found that the region of the brain associated with aggression and sex is the ventromedial hypothalamus. A research team led by Dr. David J. Anderson of Caltech examined the activity of neural circuits within the ventromedial hypothalamus of mice to explore whether certain aggression and mating behaviors that are considered instinctive are truly hard wired rather than learned. The study was supported in part by NIH’s National Institute of Mental Health (NIMH). Results were published on October 18, 2017, in Nature.

The research team genetically modified neurons in the ventromedial hypothalamus so that the cells would glow when activated. A tiny fluorescence microscope attached to the mouse’s head captured images of glowing neurons. This imaging technology enabled the researchers to tell which neurons were associated with attack or mating behaviors.

Each day, the male mice, which had never seen a mouse from another litter, were briefly introduced to five different female intruders and five different male intruders. On the first day of testing, the male mice tended not to mount or attack any strange mouse placed into its cage, and the same neurons were activated by both male and female intruders. On days 2 and 3, the research team observed separate sex-specific neural circuits in response to male and female intruders. At this point, the previously isolated male mice were more likely to attack intruder males and mate females. This finding suggests that although fighting and mating behaviors are instinctive, they require that the mouse’s brain learn to distinguish between males and females. Thus, even instinctive behaviors can incorporate a learned component.

The team also studied the effect of allowing isolated male mice to socialize with a female mouse for 30 minutes. That experience was sufficient for these male mice to either fight or mate when presented with a male or female intruder, respectively, and to develop sex-specific neural circuits. This finding suggests that socialization with a female alone is sufficient for triggering attack behavior with an intruder male mouse.

“We are studying the nature versus nurture problem: how much of the brain’s wiring and the animal’s behavior is determined by genetics versus experience,” Anderson explains. “These results reveal that even the circuitry for supposedly innate behaviors is not as hardwired as previously thought. This finding raises a whole new set of questions about how exactly social interactions with female mice can cause a change in patterns of brain activity and promote aggressiveness.”

Understanding how a healthy nervous system works to produce certain behaviors will help shed light on problems that can lead to brain disorders. This research could lead to new ways to prevent and treat these conditions.

—by Geri Piazza