Summary: Researchers identify a little-known group of amygdala-region neurons as a key driver of aggressive behavior and emotional arousal in mice, shedding light on neural mechanisms that may underlie anger.
Source: Zhejiang University
When people are provoked or threatened, anger can arise suddenly and sometimes leads to aggressive actions. Across the animal kingdom, aggression—behaviors such as chasing, biting, or attacking—serves as a core strategy for survival. Understanding how the brain initiates and regulates these behaviors is essential to understanding both normal and pathological aggression.
A study published this week in Neuron by researchers at Zhejiang University reports the discovery of a previously overlooked brain circuit that broadly controls aggressive responses in mice. The work identifies the posterior substantia innominata (pSI), a subregion associated with the amygdala, as a central node that can trigger aggressive arousal and a wide range of attack behaviors.
Although scientists have mapped neural circuits for specific forms of aggression, the mechanisms by which the brain generates a general, overarching aggressive state have remained unclear. The Zhejiang University team found that the pSI can mediate multiple types of aggressive behavior and that its activity predicts and drives the animal’s transition into an aggressive state.
“Roar” of neurons before and during conflict
The substantia innominata—literally “unnamed substance”—is one of the more enigmatic regions of the brain. In mice it is substantial in size and contains more cells than some nearby regions, yet it has received relatively little attention. “As a conserved part of the amygdala complex across species, pSI has been neglected for a long time,” says Zhenggang Zhu, Ph.D., first author and a graduate student in Shumin Duan’s lab (now a postdoctoral researcher at Janelia Research Campus/HHMI).
The researchers discovered by chance that neurons in the posterior substantia innominata became highly active when two male mice first met and engaged in fighting. Using optical calcium imaging to record pSI activity during social encounters, the team observed that neural activity in this region often rose before physical aggression began. “The ramping activity in pSI predicted whether the animal would launch an attack,” explains Shumin Duan, the study’s corresponding author.
The brain’s armed forces: pSI drives rapid attacks
To test causality, the team used optogenetics to activate pSI neurons that project to the midbrain periaqueductal gray (PAG). Photostimulation of this pSI→PAG pathway instantly switched mice from a calm state to an aggressive state: animals showed signs of arousal (pupil dilation, faster breathing, elevated heart rate, and body tremors) and launched immediate, vigorous attacks.
Notably, this induced aggressiveness was broad and indiscriminate. The light-activated animals attacked in as many as 13 different contexts—regardless of opponent size, sex, or social role (including pups or prey). “Stimulating this circuit is like mobilizing an internal ‘armed force’ that drives uncontrollable or inappropriate aggression,” says Yan-qin Yu, another corresponding author.
Linking threat, arousal, and aggression
Charles Darwin proposed that aggression and anger are evolutionarily conserved traits. In humans, provocation commonly elicits anger and can sometimes lead to violent acts. The Zhejiang team showed that rodents also display a graded relationship between threat and aggression: increasingly intense threats raised the likelihood of attack. Recordings of pSI neurons revealed that this region encodes different threat intensities with distinct activity patterns, suggesting that pSI activity reflects both the salience of external threats and the animal’s internal aggressive state.
“We found a close, graded relationship between threat signals and aggressive responses. The excitability of pSI neurons allows us to read out an animal’s aggressive arousal and the anticipated topography of aggression,” says Yan-qin Yu.
Curbing the urge to attack
Because excessive or uncontrolled aggression can cause serious harm, the team also tested whether suppressing pSI activity could reduce attacks. Using optogenetic inhibition to silence pSI neurons, they observed a marked decrease in aggressive behavior: previously irritable mice became calmer and engaged in fewer attacks. Importantly, inhibiting pSI did not impair other social behaviors such as mating, indicating a selective role for this circuit in aggression.
Given that the substantia innominata is a conserved structure across mammals, these findings raise the possibility that a homologous circuit could contribute to pathological aggression in humans. Mapping how pSI neurons encode threat and drive motor outputs through midbrain targets like the PAG provides a foundation for future research aimed at understanding and potentially treating maladaptive aggression and violent behavior.
About this aggression research news
Neuroscience News acknowledges Zhenggang Zhu for submitting this research summary for publication on the site.
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.
Abstract
A substantia innominata-midbrain circuit controls a general aggressive response
Highlights
- • pSI neuronal dynamics reflect aggressive state and the topography of aggression
- • The pSI–PAG circuit promotes arousal and elicits 13 distinct aggressive behaviors
- • The pSI controls various aggressive behaviors in an activity-level–dependent manner
- • Inactivation of the pSI circuit suppresses diverse aggressive behaviors but does not block mating
Summary
Aggressive behaviors are widespread and evolutionarily important, but uncontrolled or pathological aggression can have severe consequences. While neural pathways for specific aggressive acts have been identified, the circuits that generate a general aggressive state were previously unknown. This study demonstrates that pSI neurons respond to aggression-provoking cues with graded dynamics that predict both the animal’s aggressive state and the pattern of forthcoming aggression.
Activation of pSI neurons projecting to the periaqueductal gray increases arousal and robustly initiates or enhances multiple types of aggressive behavior in an activity-level–dependent way. Conversely, inactivation of the same pSI circuit largely blocks diverse aggressive behaviors without affecting mating.
By encoding a general aggressive response, the pSI–PAG circuit appears to act as a universal driver of multiple attack behaviors and may offer a potential target for interventions aimed at reducing pathological aggression in humans.