December 23, 2020
Love and Hate in the Mouse Brain
Sporting dogs sometimes make clumsy movements against your leg, which is usually related to the animal's sexual arousal, but not always. Recent research by neuroscientists at San Francisco City University has found that in the brains of mice, there is sometimes a fine line between love and hate (or anger).
"Our lab is interested in understanding how social behaviors and underlying emotional states are controlled by the brain," explained Dr. Thomi Carrigo, a postdoctoral researcher at San Francisco City University. "When we studied the social behaviors of mice, we sometimes noticed that male mice would mount other male mice in a manner similar to how they mount female mice," Carrigo said.
It is still unclear whether these male mice are attempting to mate with other males because they mistakenly identify them as females, or if they are aware that it is a male but are trying to establish dominance over it. The researchers wanted to understand whether the male mouse mounting another male reflects different intentions compared to mounting a female mouse, and how mounting behaviors are regulated in the brain.
To find out, the researchers first recorded videos of male and female mice climbing onto each other. They used machine learning (a type of software that learns and adapts through experience) to analyze the videos to see if there were any differences in mounting behavior depending on whether the target was male or female. The machine learning analysis showed no significant differences in the mechanics of mounting behavior.
The researchers then looked for other behavioral clues that might differentiate between male-targeted and female-targeted mounting.
One clue was that male mice "sing" when mating with female mice. These ultrasonic songs are too high-pitched for humans to hear but can be detected using a special microphone. Carrigo and her team found that male mice only sing to female mice, not to other males. Additionally, when a male mounts another male, the two animals typically engage in a fight shortly after the mounting. This does not happen when a male mounts a female partner.
These findings suggest that mounting behavior directed at females has a different meaning than that directed at males. Specifically, male-to-male mounting may represent a display of dominance or mild aggression (aggressive mounting), rather than reproductive (or affiliative) behavior.
Next, the researchers investigated which brain regions are responsible for each type of mounting behavior.
When male mice mounted either male or female mice, the researchers observed neural activity in the hypothalamus, the part of the brain that controls behaviors such as hunger, thirst, metabolism, and defense. Specifically, two regions of the hypothalamus seemed to be involved: the medial preoptic area (MPOA) and the ventromedial hypothalamus ventrolateral subdivision (VMHVL). When a male mouse mounted a female, the MPOA showed high activity, and the male would sing to the female; in contrast, when a male mounted another male, the VMHVL showed high activity, but the male did not sing to the other male.
The research team then closely examined the activity of individual neurons in the MPOA and VMHVL. They found that different groups of neurons were activated during reproductive mounting and aggressive mounting in each brain region. Furthermore, the researchers discovered that they could train a computer to correctly predict whether a mounting was sexual or aggressive based solely on the patterns of neural activity in these two regions.
The researchers then tested whether these brain regions actually control the two types of mounting behaviors or if their activity was merely associated with these behaviors. They used a technique called optogenetic stimulation, where light is used to trigger neuron activation. By directing light into specific brain areas, the researchers could induce neural activity in those regions and, in turn, induce behaviors.
When the researchers presented a female mouse to a male mouse, the male began to sing and mate with the female. However, when the researchers stimulated the male's VMHVL, the male stopped singing and began displaying aggressive behavior toward the female. Conversely, if a male mouse was displaying aggressive behavior toward another male and the researchers stimulated its MPOA, the aggressive mouse would stop fighting, start singing, and attempt to mate with the other male.
"In this study, we used mounting behavior as an entry point to understand the underlying neural mechanisms that control emotional or motivational states," Carrigo said. She added that their findings help us understand how the brains of mice, and more broadly, the brains of mammals, control emotions, and that one day, they might help us better understand human behavior.