Thursday, December 25, 2008

The Male Brain and The Female Brain Get Confused


For some, the term “neural conflict” might arouse images of severe headache pain or perhaps situational conundrums such as whether or not to have just one more piece of chocolate cake. However, I define neural conflicts in terms of brain circuits that function in opposition to each other, such that, in many situations, both systems cannot be actively commanding an individual’s behavior at the same time. For example, you cannot be awake and asleep at the same time, nor can you be hungry and satiated, or both suffering miserably and reviling in hedonistic pleasure. In this entry, I highlight a bizarre form of neural conflict….a conflict between the male side of the brain and the female side of the brain. Differences in the mental functioning of men versus women are touchy subjects, but remain a vigorous area of research. Over the years subtle differences have been suggested. Many of us are familiar with concepts that emerged from psychology regarding the male bias towards spatial and logical/mathematical reasoning versus the female bias toward emotional and verbal skills. Indeed, these famous studies laid the foundation for a theory called the “male brain hypothesis” for the underlying causes of autism, a spectrum of neurological disorders in which social behaviors are impaired, but spatial and mathematical skills are normal or sometimes remarkable. Simon Baron-Cohen suggested that autism spectrum disorders, which are more common in males and characterized by impaired social behaviors, might represent an overtly male brain. In addition, subtle differences in brain size have been observed, with men having a slightly higher percentage of white matter (myelinated areas, see image above) and women a slightly higher percentage of grey matter (see image above, Allen et al., 2003). Further, some regions, such as a structure in the preoptic area of the hypothalamus, appear to be larger in males than females. However, after decades of work we know little about why one person thumps their masculine chest, while another gets in touch with their feminine side. There is no penis like structure hanging off the front of the male brain that explains it all.

After years of research looking for differences between males and females, who would have guessed that the circuits for male and female behavior are both residing happily together in the same brain. That is what is suggested by Catherine Dulac’s study in Nature (Kimhi et al. 2008). They present evidence in mice that in a given individual both male and female circuits exist simultaneously and propose that switches at the level of neuronal circuits regulate incoming sensory information and channel it to the male circuits, if you are a male, and to the female circuits, if you are a female. Their evidence is striking (see the movie below). They used genetic manipulations to silence the sensory "switch" in the brains of female mice. Specifically, the mice were engineered so that an ion channel in their vomeronasal system is deleted so that this organ does not work. The vomeronasal system does not exist in humans, but acts sort of like the sense of smell for rodents and many other animals, primarily to detect pheromones and other social cues. As shown in the attached movie, the female mice with the silent switch and impaired ability to interpret phermones begin to behave like male mice. Remarkably, they mount and fully copulate with other females and males, even though they don’t have a penis.

This is a striking example of neuronal circuits existing in functional conflict with each other. The inappropriate activation of male circuitry in the female brain, resulting from a disruption in the processing of sensory information (pheromones), leads to an inappropriate male-typical pattern of behavior. Identifying the identity and organization of male-typical and female-typical circuits and how they interface with circuits that communicate sensory information from the environment to the brain will be a critical future direction.