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When defending their territory, male mice typically appear threatening before launching an attack, ensuring that aggression does not unnecessarily escalate. Researchers at the University of Tsukuba found that increased activity in the neural pathway going from the lateral hypothalamus (LH) to the dorsal raphe nucleus (DRN) boosts attack behavior without affecting threat displays.

Tsukuba, Japan—For many animals, aggression is essential for territorial defense. However, excessive aggression increases the risk of serious injury. To prevent escalation, animals such as male mice frequently employ threat displays to show their strength before biting. Previous research has shown that this balance can be disrupted in mice exposed to early-life stress, leading to disproportionate biting attacks. In this new study, the researchers investigated the brain mechanisms that help maintain the balance between intimidation and physical aggression.

The researchers found that projections from the LH to the DRN are critical for preserving this behavioral balance. Experimentally increasing the activity of this pathway increased the occurrence of attacks—particularly, stronger "hard bites"—, without affecting threat displays. Conversely, inhibiting the pathway decreased attack bites leaving threat behaviors unaffected. Further, mice avoided behaviors that activated this pathway, suggesting that its engagement may induce an aversive internal state.

Despite obvious differences between humans and mice, people can become irritable or unexpectedly aggressive under intense stress. These findings provide insights into how stress and negative emotions may fuel intense or maladaptive aggression, helping inform future research on the neural basis of stress-related aggression.

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This study was supported by Japan Society for the Promotion of Science (JSPS) DC-2 Grant Number 24KJ0492 (K.M.), Japan Science and Technology Agency (JST) FOREST Program Grant Number JPMJFR214A, JSPS KAKENHI Grant Numbers 22K19744, 22H02660, and a research grant from the Astellas Foundation for Research on Metabolic Disorders (A.T.).

Original Paper

Title of original paper:

Lateral hypothalamus to dorsal raphe nucleus projections modulate intraspecific attack behavior in male mice

Journal:

iScience

DOI:

10.1016/j.isci.2026.115427

Correspondence

Associate Professor TAKAHASHI Aki
Institute of Human Sciences, University of Tsukuba

MITSUI Koshiro
Doctoral Program in Neuroscience, Degree Programs in Comprehensive Human Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

Related Link

Institute of Human Sciences