Researchers have discovered that distinct clusters of brain cells in mice act like on and off switches for gender-specific social behavior. This cluster is permanently turned on in females, but remains silent in adult males until mating. This strictly dualistic brain feature provides new insights into how social and reproductive life stages physically change the brain. The results of this research have recently Proceedings of the National Academy of Sciences.
There are obvious physical differences between male and female bodies in anatomy and hormones. Biologists refer to these sex-based physical differences as sexual dimorphism. In the brain, these physical distinctions are usually less clear and very difficult to categorize.
Most of the differences between men and women in the brain appear as overlapping gradients rather than the presence or absence of exact characteristics. Although certain brain regions may be slightly larger or have more connections in one gender, there are still many similarities between the two groups. It is extremely rare for truly binary differences to exist in the brain.
Tamar Licht and Dan Rokni of the Hebrew University of Jerusalem wanted to find out whether there are absolute differences in the way brain cells behave at rest. They led a team of researchers looking for neurons that were active in one sex, but completely silent in the other.
The researchers focused on an area called the medial amygdala. This is a small structure deep in the brain that helps animals process emotions, interpret social signals, and manage reproductive behavior. It acts as a central hub for integrating odors and other sensory signals from the environment, allowing the animal to respond appropriately to rivals and potential mates.
To find out which cells were active, the researchers tracked specific genes that were turned on immediately after neurons fired. These genes act like genetic markers that indicate that a cell has recently communicated with other cells. Biologists often use these genes to map which parts of the brain are functioning during specific behavioral tasks.
The researchers used genetic tracking tools to permanently tag active neurons in living mice. When mice were given a specific trigger drug, the brain cells that fired at that exact moment were permanently labeled with a bright red fluorescent protein.
The technique allowed the team to view brain slices under a microscope after a few weeks. They were able to easily identify which cells were active during the tagging process, even if the cells went quiet afterwards.
When Licht and his colleagues examined the medial amygdala, they noticed that the female mice had dense circular clusters of light-emitting cells. They named this cluster DIMPLE, in part because it resembled facial dimples on both sides when looking at slices of the brain.
This glowing cluster appeared in every female mouse they tested. In contrast, it was completely absent in nearly 100 virgin male adult mice. Cellular activity represented a complete dichotomy between the sexes.
“Most sex differences in the brain are subtle and distributed,” says Dr. Licht. “What struck us here was the clarity of the signal: it’s a discrete group of neurons acting almost like a biological switch, reflecting gender and social state in a very robust way.”
The researchers then tested whether removing adult reproductive hormones changed this pattern. They surgically removed the ovaries from female mice and the testicles from male mice.
They waited a month for hormone levels to drop, then tagged the brain cells again. Shining dimple clusters still appeared on all women, but not on men. This indicates that baseline adult sex hormones do not maintain this difference.
The researchers then looked at young mice to see when this difference appeared. They tagged the brains of adolescent mice before separating the pups from their mothers.
At this young age, dimple clusters were active in both men and women. Male activity disappears only after the male grows up and leaves the family unit, suggesting that the social environment influences the cells.
The researchers then investigated whether social or reproductive experiences could cause the clusters to recur in adult men. They put adult virgin males in cages with females and let them mate.
When the researchers tagged the male brains shortly after mating, the DIMPLE cluster suddenly lit up. The cells were activated again after one reproductive encounter.
The researchers conducted several tests to see exactly what caused this change in the men. Even when males were allowed to smell the female’s bedding or interact with her through a transparent barrier, no brain cells were activated.
The cluster was only turned on when the male had physical sexual contact with the female. The cells remained active as long as the male remained in the cage with his pregnant partner.
When the males were removed from the cage a few days after mating, the clusters darkened again. Brain activity requires the continued presence of females, indicating that clusters dynamically respond to the animal’s current social status.
Copulation causes the release of certain chemicals in the body, so the researchers thought hormones might be involved. They focused on prolactin, a hormone well known for stimulating milk production and promoting parental behavior.
In normal physiological settings, prolactin levels naturally rise in male mice immediately after mating. When the researchers injected virgin male mice with prolactin, the DIMPLE cluster turned on even in the absence of female contact. This suggested that prolactin alone could activate these specific brain cells.
The researchers then tried blocking prolactin in mating males and females to see if the clusters would be turned off. They added a drug to the mice’s drinking water that stopped the release of prolactin from the pituitary gland.
The drug failed to turn off the brain clusters in both groups. The researchers pointed out that either the drug did not lower the hormone enough or other chemical signals were also involved in keeping the cells active.
Although these results provide a clear example of a biological switch, the exact behavioral purpose of the DIMPLE cluster remains to be proven. Researchers think this may help prevent adult males from attacking newborn puppies.
Male mice typically exhibit aggressive behavior toward their infants, but this behavior turns into protective parenting after mating. The sudden activation of the DIMPLE cluster is fully consistent with this behavioral change.
Testing this idea is technically difficult. This cell mass is located deep within the brain and lacks unique molecular markers, making it extremely difficult to target with current experimental tools.
Future research will need to find ways to selectively turn these cells on or off to see how mice behave. Scientists also need to investigate other hormones and genes to fully understand how this brain region works.
So far, the findings show how deeply social experiences can rewire men’s brains. This provides a new starting point for understanding how animals adapt to different stages of life.
The study, “Sexually dimorphic neuronal clusters in the mouse medial amygdala responds to male sexual status,” was authored by Tamar Licht, Adan Akarieh, Aya Dhamshy, Amit Zeisel, Osnat Ophir, and Dan Rokni.
