• The brain circuitry that controls innate, or instinctive, behaviors such as mating and fighting was thought to be genetically hardwired. New findings from the Anderson laboratory suggest that this is not the case.
    Credit: Caltech

Nature or Nurture? Innate Social Behaviors in the Mouse Brain

Caltech neuroscientists image activity deep in the brain while mice engage in fighting and mating



The work appears in a paper in the October 19 issue of the journal Nature, and was led by David Anderson—Seymour Benzer Professor of Biology; Tianqiao and Chrissy Chen Institute for Neuroscience Leadership Chair; Howard Hughes Medical Institute Investigator; and director of the Tianqiao and Chrissy Chen Institute for Neuroscience.

The team used mice that had been genetically engineered so that neurons in a specific part of the brain involved in aggression and sexual behavior—the ventromedial hypothalamus (VMH)—would glow green when activated. To visualize this activation, a needle-thin glass lens was inserted into the hypothalamus, and images of flashing neurons were recorded by a miniature, portable microscope attached to the mouse's head. This brain imaging technology was originally developed by Anderson's collaborator at Stanford University, Mark Schnitzer, and obtained through Inscopix.

The Caltech team first set up "resident/intruder tests," in which they imaged the brain of a socially and sexually experienced "resident" mouse in its cage as a single intruder mouse—either a male or a female—was introduced. The researchers found that during its encounters with other mice, one of two distinct sets of neurons in the VMH were activated—one set if the other mouse was a male, and another if it was a female. Though these neurons are spatially intermingled, there is very little overlap between them, like grains of salt and pepper interspersed on a plate.



Surprisingly, to the contrary, the neurons of these naïve mice initially were similarly activated when the mice were exposed to either male or to female mice. At the same time, these mice initially exhibited little fighting (with males) or mating (with females) behaviors. Only after repeated social experience—contact with either male or female mice for two minutes, five times a day, for three days—did the separate sets of neurons representing male versus female mice appear. This separation occurred just as the mice began to exhibit aggression toward males and mating with females.


"The mice do not have sex-specific neurons from birth," says co-first author Ryan Remedios, postdoctoral scholar in biology and biological engineering. "The separation forms as a consequence of social experience, specifically from social experience with a female."

"This is an unexpected discovery," says co-first author Ann Kennedy, a Caltech postdoctoral scholar in biology and biological engineering. "This area of the brain, the ventromedial hypothalamus, is a primitive, ancient region. We used to think of it as the basement of the brain, more like a plumbing system than a computer. Our study shows that this region exhibits plasticity and computation."

"This is basic neuroscience research," says Anderson. "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. 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."


The paper is titled "Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex." Other co-authors include Caltech postdoctoral scholar Moriel Zelikowsky and Benjamin Grewe of the University of Zurich. Funding was from the National Institutes of Health, the Gordon and Betty Moore Foundation, the Ellison Medical Foundation, the Simons Foundation, the Harry Frank Guggenheim Foundation, the Helen Hay Whitney Foundation, the National Science Foundation, and L'Oréal USA For Women in Science.

Written by Lori Dajose