Summary: Study reveals the lateral habenula plays a critical role in the priming of aggression in male mice.
Source: University of Tsukuba
When male animals spend time around other males of the same species, subsequent aggressive behavior tends to be amplified—this type of priming is known as social instigation. However, the pathway in the brain that leads to this increased aggression was, until recently, relatively unknown.
In a study published in Nature Communications, researchers from the University of Tsukuba have revealed that the lateral habenula, a small and relatively primitive region located deep within the brain, is important for this behavior in mice.
Aggressive behavior, especially between males, is important in many animal species and can be promoted in a number of different ways, including by social instigation.
Although this behavioral effect is well characterized, the brain pathway that is responsible for it is less understood.
The dorsal raphe nucleus is a brain region that controls aggressive behaviors, and it receives glutamate (a molecule that acts as a signal between brain cells) when social instigation occurs. However, the source of this glutamate was a mystery.
Researchers from the University of Tsukuba decided to address this gap in the knowledge.
“Many different brain regions release glutamate into the dorsal raphe nucleus,” explains lead author of the study Professor Aki Takahashi.
“Because our initial experiments suggested that glutamate release from the lateral habenula might be responsible for aggression induced by social instigation, we conducted more experiments to see if this was the case.”
The research team used two different techniques to block communication between the lateral habenula and dorsal raphe nucleus in mice, and found that this also blocked the increased aggression caused by social instigation—but it didn’t affect normal levels of aggression, suggesting that this pathway is not important for aggressive behavior in general.
“We then wanted to look at the pathway beyond the dorsal nucleus,” says Professor Takahashi.
“We found that social instigation caused signals to travel through the brain from the lateral habenula to the dorsal raphe nucleus and then on to the ventral tegmental area—a highly connected region in the midbrain—leading to heightened aggression.”
Although there are many differences in aggression between humans and mice, the results of this new study may have applications when investigating socially provoked anger or violence. There is currently a lack of effective preventative measures against socially provoked aggression, and any information that increases our understanding of these aggressive behaviors will be useful.
Funding: This research was supported by JSPS KAKENHI Grant Numbers JP17H04766, JP19H05202, JP21H00183, Japan Science and Technology Agency (JST) Adaptable and Seamless Technology transfer Program through Target-driven R&D (A-STEP) Grant Number JPMJTM20BW and JST FOREST Program Grant Number JPMJFR214A to AT, and by National Institute of Mental Health grants R01MH114882-01, R01MH104559, and R01MH127820 to SJR.
About this social aggression and behavior research news
Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice
The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice.
Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse (“social instigation”) resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice.
In contrast, inhibition of this pathway did not affect basal levels of aggressive behavior, suggesting that the activity of the LHb-DRN projection is not necessary for the expression of species-typical aggressive behavior, but required for the increase of aggressive behavior resulting from social instigation.
Anatomical analysis showed that LHb neurons synapse on non-serotonergic DRN neurons that project to the ventral tegmental area (VTA), and optogenetic activation of the DRN-VTA projection increased aggressive behaviors.
Our results demonstrate that the LHb glutamatergic inputs to the DRN promote aggressive arousal induced by social instigation, which contributes to aggressive behavior by activating VTA-projecting non-serotonergic DRN neurons as one of its potential targets.