A lingering question asked by neuroscientists has to do with what, if anything, makes the male and female brains distinctive, whether in mice or (wo)men. There is still no concise answer. The best evidence from the most recent research suggests that both males and females share the same neural circuitry, but use it differently. Catherine Dulac, a professor of molecular and cellular biology at Harvard, and investigator at the Howard Hughes medical Institute, is a pioneer in exploring these questions. I talked to her briefly about her research, which also extends far beyond just the neurobiology of gender.

Can you tell me in broad overview about what you study?
I'm interested in understanding how the brain engages in instinctive social behaviors. There are a lot of instinctive behaviors such as eating and sleeping that are essential in animals and humans, but social behavior is a very distinctive and particularly interesting set of instinctive behaviors that we would like to understand at the neuronal level.

What we would like to understand in mechanistic terms is how does an individual recognize other animals of its own species, for example how does an animal identify as a male, a female, or an infant, how does the brain process these signals in order to trigger appropriate social behaviors such as mating, aggression or parenting.

Can you tell me a little bit about your work of the last few years that relates to gender identification?

Catherine Dulac
Credit: MCB graphics, Harvard University

One characteristic of social behavior that is absolutely fundamental is that males and females in all animal species behave differently when they encounter a given social signal. So, for example, if one observes parental behavior, in many species females are spontaneously maternal: they will nurse and take care of infants, in contrast to males, which in most species are infanticidal, meaning they will just attack infants when they enter a social group that is not their own. In turn, males in many species become paternal once they sire their own offspring

So why is that? What underlies these sex differences in behavior? Do males and females detect various stimuli in different ways or do they detect the same stimulus but then have a different neural processing of social signals in the brain. To understand social behavior in mechanistic terms, it is absolutely essential to understand how different the male and female brains are. That question has occupied us a lot recently, and we came across some initial answers that are extremely interesting and surprising.

Indeed, it is assumed that the male and the female brains are very different because males and female behaviors differ so significantly. But over the last few decades, neuroscientists have been looking for major anatomical differences and did not find that many. Actually, they've found surprisingly few differences: more neurons or more neuronal spines here and there in one sex or the other, with great variations from one individual to the other but that’s about it. So there is a paradox between this apparent similarity of the brains of males and females and the strikingly different behaviors they engage in.

We've been looking at this paradox and I think we've found some very intriguing ideas—that there are few dedicated parts of the brain that are different between males and females, but most of the brain, including key areas engaged in the control of social behaviors, are likely to be very similar. So, for example, we discovered a set of neurons in mice that control maternal behavior and these neurons are also found in male brains although males are not spontaneously paternal. However, if these neurons are specifically activated in males, they become as parental as mom can be.

Has there been any change in existing hypotheses about what gender is?
To a large extent yes. There was really an assumption that from birth animals, including humans, are already set in having neuronal circuits that are established as either male or female. As it turns out, we don’t think this is the case. We think that, to a large extent, both males and females have both male-and-female neuronal circuits, but these circuits are regulated in a sex-specific way, which provides some important behavioral flexibility.

Our finding is not revolutionary in any way. Ethologists—people who were studying animal behaviors in the 1920s, 1930s and 1940s—had observed that both males and females could occasionally display the behavior of the other sex. At that time they were obviously surprised. But then there followed a phase when things became more black and white—and it was thought that your brain is built as either male or  female and all that is under the very early control of steroid hormones.

Our work somehow challenges these set of hypotheses, which have been the dogma for the last 50 years or so. But our work also fits well with way older observations of ethologists before the discovery of steroid hormones and the acceptance of this black-and-white idea of what the male brain and female brain are.

Has your work attracted interest from the lay community, the non-scientist community?
I was extremely worried that our work would be misinterpreted and that work from the mouse would be immediately thought of as applying to humans. I'm a basic neuroscientist and so when we published our work in top journals many years ago, I was very careful that our work was not hyped, so that I could continue our fundamental work without interference from wild interpretations. There was the understanding that maybe at some point when we have a better understanding of what's going on then we would be able to speak more intelligently about its meaning across animal species. It is only very recently, for example when I was invited to participate in two Charlie Rose shows [one, two] that I think I was able to convey the state of the science on some of these issues on parenting behavior and gender identity. I think we’ve reached a level that lets us reach out to the larger public in ways that I was absolutely not able to before.

What are some of the overarching questions you'd still like to answer based on what you've found?
I would say that we've moved through a couple of steps, but what lies ahead is really an understanding of how behavior is controlled in a mechanistic way. What does control mean? How does the brain engage in the different steps constituting parental or mating behavior? What are the different components of how these behaviors are executed and regulated? Why are these same neurons active in females and not in males in certain physiological circumstances, but that difference disappears in other physiological circumstances?

Also, how does the environment affect the function of neuronal circuits? All of this has a lot of implications, not only to understand how behavior works in terms of neurons and molecules but also for potential ways to understand and potentially cure mental disorders. Social behaviors are profoundly affected in mental disorders such as depression, schizophrenia, autism etc. Parenting behavior, for example, is associated with a very prevalent disorder called postpartum depression. It affects 10 to 20 percent of women and 5 and 10 percent of fathers. If we understand how the control of parenting works, maybe we'll find ideas on how to help such patients.