Getting the Inside Dope on How We Get Angry | Nutrition Fit



Summary: Little-known amygdala cells are identified as the key mediator for aggressive behaviors and may drive our angry.

Source: Zhejiang University

When human beings are provoked and threatened, anger often arises spontaneously and is even accompanied by certain aggressive behaviors. In the chain of the biological jungle, aggressive behaviors (includes hunting, chasing, and biting) are the core strategy of survival of the fittest for animals.

In a study published this week in Neuron, researchers from Zhejiang University have revealed that a novel brain circuit controls a general aggressive response, including trigger all fights and drive aggressive arousal in the mouse.  

Most animals, including humans, will evolve specific brain circuits to execute and control aggressive behavior. But how does the brain manages anger and precisely regulates aggressive behavior remain unclear. But now, researchers from Zhejiang University found that a little-understood region – posterior Substantia Innominata (pSI), can mediate the expression of various types of aggressive behaviors and trigger affective aggression. 

 ‘Roar’ of brain cells before and during a fight

The substantia innominata, like its name – an un-named substance, is one of the most mysterious regions in the brain. But in mice, it is larger than the lateral hypothalamus and has more cells than the central amygdala. “As a conversed region in the amygdala of the human and mouse brain, we have neglected it for a long time,” says first author of the study Zhenggang Zhu, Ph.D., a graduate student in the Shumin Duan’s lab and current postdoctoral researcher at Janelia research campus/HHMI.

“Accidentally, we found the posterior part of the substantia innominata (pSI) were extremely active after two mice met and fought,” says the corresponding author of the study Shumin Duan. “We recorded the cell activity of the posterior substantia innominata using advanced optical calcium imaging. Interestingly, We proved that the neural activity even ramped before the battle. Whether the further attack will launch or not can be predicted by the cellular activity of the pSI.”

The armed forces in the brain

By activating pSI neurons projecting to the periaqueductal gray of the midbrain through the optogenetic stimulation, the team was excited to see these cells trigger attack actions in seconds. “The photostimulation instantly switched the mouse from the “peaceful state” to “fighting state”: aggressive arousal (pupil dilation, faster breathing, increased heart rate, and body trembling) and intensive fights are immediately evoked in the mouse,” says another corresponding author of the study Yan-qin Yu.

More importantly, no matter facing a stronger enemy, or the opponent changes (from preys to pups, or females), different genders, as many as 13 different situations in total, the lighted mouse will attack the opponent without any hesitation. “This activation is similar to mobilizing and invoking “the armed forces in the brain,” leading to some uncontrollable and inappropriate aggressive displays,” says the first author of the study Zhenggang Zhu.

Unveiling the mystery of “anger”

Darwin said: “aggressive behavior and anger in animals and humans are evolutionarily conserved.” Human beings not only retain a variety of forms of aggression instinct, the expression of aggression is also often accompanied by the burst of anger. Notably, provocation can arouse human anger and even induce violence. “Interestingly, our team demonstrated that the relationship between threat and attacks also applies to rodents: the graded intensity of threats gradually increased the probability of mouse aggression.” 

This shows a kid making a fist
Most animals, including humans, will evolve specific brain circuits to execute and control aggressive behavior. Image is in the public domain

“We surprisingly found that Relationship between threat stimuli and aggressive response is so closed. Additionally, pSI neurons encode different intensities of threat stimuli through the recording of pSI neuronal activity”, Said Yan-qin Yu, “we should be able to read out the salience of “aggressive state” from the excitability of the pSI in the mouse.”

Curb the attack urge

Once the anger is out of control, it may produce excessive and morbid attacks and bring great harm to society. How to diminish the aggressive behaviors became the next important goal for the whole team. Thus, the group carried out the optogenetic inhibition on the pSI cells and found the irascible mice suddenly became mild and less aggressive when pSI silenced. Remarkably, the inhibition of pSI neurons did not affect other social activities of the mice. 

Given that the substantia innominata is a conserved region in the human brain, this research opens the door to new investigations of the role of the amygdala in human pathological aggression. Understanding how pSI neurons process and transmit information is critical to digging the inside dope on how we get angry and understanding the mechanisms of violence.

About this aggression research news

Neuroscience News would like to thank Zhenggang Zhu for submitting this research article for inclusion on the website.

Source: Zhejiang University
Contact: Zhenggang Zhu – Zhejiang University
Image: The image is in the public domain

Original Research: Closed access.
A substantia innominata-midbrain circuit controls a general aggressive response” by Zhenggang Zhu et al. Neuron


See also

This is a diagram of toddlers eating

A substantia innominata-midbrain circuit controls a general aggressive response


  • pSI neuronal dynamics reflect aggressive state and the topography of aggression
  • The pSI-PAG circuit promotes arousal and elicits 13 aggressive behaviors
  • The pSI controls various aggressive behaviors in an activity-level-dependent manner
  • Inactivation of the pSI circuit blocks diverse aggressive behaviors but not mating


Although aggressive behaviors are universal and essential for survival, “uncontrollable” and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown.

Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice.

Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity-level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors but not mating.

By encoding a general aggressive response, the pSI-PAG circuit universally drives multiple aggressive behaviors and may provide a potential target for alleviating human pathological aggression.


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