Nature, not nurture: New evidence in mice that recognition of a stranger’s sex is baked into the brain at birth

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Image by Elizabeth Kunker, courtesy of the Shah lab

By Bruce Goldman

Male mice are hardwired to recognize the sex of other mice, a new study in Cell shows. No previous experience required. Female mice also catch on quickly to a stranger’s sexual identity, but researchers haven't figured out yet where the brain circuitry guiding those decisions resides.

The findings add fuel to one side of a longstanding debate, carried on largely between bioscientists and social scientists, about the relative influences of hardwired versus socially acquired influences on sex-specific mammalian behaviors. (That debate was the central subject of "Two Minds: The Cognitive Differences between Men and Women," an article I wrote for our magazine, Stanford Medicine, in 2017.)

In the new study, molecular neuroscientist Nirao Shah, PhD, and his Stanford colleagues pinpointed, for the first time in mammals, a small but essential set of neurons in the male mouse brain that drive even a sexually inexperienced animal’s ability to speedily determine another’s sex. The researchers used sophisticated genetic techniques that allowed them to remotely switch these neurons on and off at will and to observe the behavior that ensued in controlled social situations. Not the type of experiment you can do in people.

But this discovery is likely to be relevant to us humans, Shah told me, because, being mammals ourselves, we share with mice much of the same brain circuitry they use for recognizing a stranger’s sex — and, importantly, because human studies of this circuitry indicate substantial structural and physiological differences between men and women.

The brain structure that houses the nerve-cell circuitry governing male mice's ability to distinguish between the sexes is called the "bed nucleus of the stria terminalis." In humans, that structure is twice as large and more densely populated with neurons in men than in women, and studies have revealed different patterns of gene-activation levels in men versus women — a reliable clue that its function differs by sex.

It’s long been known that a male mouse on its own turf, whether it’s sexually naïve or experienced, responds predictably to the intrusion of another mouse. That response depends on the stranger’s sex: If it's a male, the mouse will pick a fight, while he'll try to mate with a female.

“All social and sexual encounters are predicated on first correctly identifying the sex of the other agent,” Shah said. “It’s a fundamental decision animals make."

So, maybe not such a good idea to leave it to chance. From my news release about the study:

In its lifetime, a wild male mouse may get just a few shots at sexual reproduction, ratcheting up the advantage of being able to correctly identify a newcomer’s sex in short order without having to learn how first. If that ability is innately programmed, even a sexually inexperienced mouse can rapidly discern males from females of its species.

It makes strong evolutionary sense for the mammalian brain not to be a so-called "blank slate," equally accessible to every experiential piece of chalk that comes along to write on it, but rather for some behavioral patterns to be genetically hardwired — and for the most hardwired behaviors of them all, such as reproduction, to be the ones most mission-critical to species' survival. In Darwinian terms, that's the successful generation of . . . well, of the next generation. 

Having co-evolved for hundreds of millions of years, the two sexes have acquired differing reproductive strategies, with resulting divergent yet complementary behaviors. After all, why would evolution come to a screeching halt above the neck?