A brain circuit that reduces male hostility when an opponent has a physical edge.

Neuroscientists have attempted to comprehend the neural mechanisms underlying various social behaviors, including aggression, for decades. Forceful, fierce, or angry ways of behaving are normal among people and numerous creature species, yet the brain processes supporting or stifling these ways of behaving have not been completely revealed at this point.

An area in the hypothalamus, a region of the brain that influences the nervous system and the release of hormones, that suppresses aggression in male mice when they are confronted by an opponent who is stronger or physically “superior,” has recently been discovered by researchers at New York University Langone Medical Center. Their research, which was published in the journal Nature Neuroscience, shed some fresh light on the neural pathways that control aggression in animals and, possibly, humans.

One of the study’s authors, Dr. Dayu Lin, told Medical Xpress, “I have been studying aggression circuits in mice since I started my lab in 2010.” Beforehand, we observed that VMHvl is a fundamental district for creating hostility, so we had our eyes on this region for some time. Although MPOA is the top region that projects to the VMHvl, its function in aggression is unknown because it has traditionally been regarded as a key region for sexual behaviors.

“This is critical for the survival of all animals, including humans, because misdirected aggression can have serious, even fatal, consequences. We also discovered that the cMPOA cell responses are very changeable after a social experience of loss.”

Dr. Dayu Lin, one of the researchers who carried out the study, 

Lin and her colleagues discovered that when mice were socially interacting with one another, the rostral (or frontal) and caudal (or posterior) parts of the MPOA, which is a part of the hypothalamus, responded differently. They discovered that interactions between male and female mice caused the caudal MPOA to be more active than those between male and female mice.

Lin stated, “We found that aggression was strongly suppressed when we manipulated the caudal MPOA.” At that point, we considered the likely circumstances under which male hostility towards another male could be smothered. As a result, we discovered that when a male fights a stronger opponent, cMPOA cell activity rises.”

To direct their new investigations, the specialists utilized a blend of optogenetic and chemogenetic procedures. Using fiber photometry, an optogenetic method, they collected patch clamp recordings in mouse brain slices and recorded calcium activity in the mice’s brains.

A patch clamp recording method involves connecting a recording electrode to an amplifier that touches isolated cells after filling a hollow glass tube with electrolyte solution. This permits specialists to quantify long-term changes in the elements of explicit neurons by taking a gander at the mind tissue of perished creatures. This method demonstrated that MPOA cells inhibit VMHvl cells by synapsing directly onto them.

Lin and her colleagues also observed the behavior of living male mice during social interactions after inhibiting or activating cells in the cMPOA using optogenetic techniques. Interestingly, activating these cells reduced the aggressive behaviors of the male mice, while inhibiting them appeared to increase their aggression toward other males.

Lin elaborated, “Our findings suggest that cMPOA cells naturally suppress aggression.” We found that cMPOA cells undertake and restrain VMHvl cells. Likewise, hindering cMPOA to VMHvl projection caused an expansion in hostility even towards more grounded guys, while actuating the pathway diminished hostility. The in vivo activity of cMPOA was then examined, and we discovered that stronger men activate the cells more than weaker men.”

Overall, Lin’s research suggests that the posterior portion of the MPOA has a significant impact on male mouse aggressiveness. By reducing activity in the VMHvl, this region of the hypothalamus appears to reduce aggression toward a more powerful male opponent.

Lin stated, “Our studies discovered a new pathway that suppresses aggression toward inappropriate targets.” Because misdirected aggression could result in severe, even fatal consequences, this is essential for the survival of animals and humans alike. After the social experience of losing, we also found that the cMPOA cell responses were highly plastic.”

This group of researchers’ most recent work sheds new light on the intricate neural mechanisms that underlie aggression and demonstrates, in particular, how the brains of mice prevent adversarial fighting. It could lead to fascinating new discoveries about how the MPOA influences aggressive behaviors in the future, which could also help clinical studies on people who have aggressive or violent tendencies.

“MPOA and VMHvl are physically dimorphic locales,” Lin added. “It will be interesting to see if females have the same circuit now. Understanding the synaptic and cellular mechanisms that cause MPOA cells to respond differently to the stronger male following defeat is another area of interest for our subsequent research.

More information: Dongyu Wei et al, A hypothalamic pathway that suppresses aggression toward superior opponents, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01297-5

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