Oxytocin pathways in the brain fuel spontaneous helping behavior in mice

A new study published in the Proceedings of the National Academy of Sciences has revealed that mice spontaneously help unconscious peers recover from anesthesia through grooming and licking behaviors. These actions, which occur without training or external rewards, not only speed up the recovery of the anesthetized mice but also appear to reduce the emotional stress of the helping mice. The research identifies two distinct brain pathways—both relying on the neuropeptide oxytocin—that regulate the emotional and motor aspects of this behavior.

Scientists have long been fascinated by acts of spontaneous helping in humans and animals. While certain species like dogs, elephants, and primates have been known to engage in helping behaviors, the extent to which rodents are capable of untrained, prosocial actions has been unclear. The current study set out to investigate whether mice could exhibit a type of altruistic behavior known as “rescue-like behavior” and to understand the brain mechanisms behind it.

“The study originated from a serendipitous observation,” explained study author Zhou-Feng Chen, senior principal investigator at the Institute of Neurological and Psychiatric Disorders at Shenzhen Bay Laboratory. “During routine experiments, a student noticed awake mice repeatedly licking and grooming an anesthetized companion in their home cage. This unexpected behavior sparked our curiosity: Why were they doing this? Further investigation revealed that such social grooming and licking appeared to accelerate the anesthetized mouse’s recovery from unconsciousness, which became the foundation of our research.”

Intrigued by this unexpected interaction, the research team began systematically studying the phenomenon. They wanted to know whether this behavior was driven by empathy-like processes, whether it helped the unconscious mice recover, and which neural circuits were involved.

To investigate, the researchers developed a new behavioral test. An awake mouse (called the observer) was placed in a chamber with a peer (the demonstrator) who had been anesthetized with ketamine. The observer typically approached the anesthetized demonstrator and began licking its face and grooming its body. These interactions were recorded on video and scored for the amount of time spent in social grooming behavior.

The team tested various conditions to see whether this behavior was specific to certain types of demonstrators. Observer mice interacted much more with live anesthetized animals than with dead mice or artificial models, suggesting that they could detect signs of life and directed their behavior accordingly.

“Mice could distinguish between unconsciousness and death, avoiding deceased companions,” Chen told PsyPost. “This implies unconscious mice may emit ‘distress signals’ to elicit help—a phenomenon reminiscent of ‘SOS’ signals.”

In follow-up experiments, the researchers found that this rescue-like behavior helped the unconscious mice regain their righting reflex—the ability to flip themselves upright—sooner than they would have without help. Electroencephalogram (EEG) recordings confirmed that mice receiving social grooming emerged from anesthesia more quickly, showing a shift from low-frequency brain waves (associated with deep unconsciousness) to higher-frequency patterns linked to wakefulness.

Chen was surprised by the dramatic effect of licking. “Anesthetized mice regained consciousness up to 30% faster when licked,” he noted.

To explore whether the observer mice were emotionally affected by the state of their peers, the researchers measured levels of corticosterone, a hormone associated with stress. Mice that could see but not touch an anesthetized cage mate had higher stress levels than those exposed to a healthy peer, suggesting that witnessing a non-responsive conspecific caused emotional distress. Giving the observer mice a drug that reduces social stress led to delayed approaches and less grooming, indicating that emotional arousal may motivate the rescue-like behavior.

At the neurobiological level, the researchers focused on the role of oxytocin, a hormone known to be involved in social bonding. Mice that lacked the gene for oxytocin showed significantly less rescue-like behavior. Using fiber photometry to track real-time brain activity, the researchers observed that oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus became active when mice approached and groomed an anesthetized peer.

To pinpoint how oxytocin influences different aspects of the behavior, the team examined two brain regions that receive projections from the PVN. The central amygdala (CeA) appeared to be involved in the emotional recognition of the demonstrator’s state. When oxytocin receptors in this region were blocked, mice showed less social grooming and took longer to approach. The dorsal bed nucleus of the stria terminalis (dBNST), by contrast, controlled the execution of the grooming behavior itself. Stimulating this area led mice to perform grooming behaviors even without a demonstrator present, while shutting it down stopped grooming altogether.

The two pathways played different roles in shaping the behavior. Activity in the CeA peaked right at the start of grooming, suggesting it functions as a trigger for the behavior. In contrast, the dBNST showed a sustained activation pattern that matched the duration of grooming. These findings suggest that the CeA helps initiate the response, while the dBNST keeps it going.

“Mice spontaneously lick/groom unconscious peers, significantly shortening their recovery time,” Chen told PsyPost. “The primary motivator for this behavior seems to be emotional stress in the awake mice, suggesting that ‘helping’ others might stem from self-preservation instincts rather than pure altruism. Reciprocal care—helping others to benefit oneself or the group ultimately—appears deeply rooted in evolution and common among social animals. This reciprocity likely strengthens communal bonds and enhances species survival.”

Despite the strengths of the study, several questions remain. It is still unclear exactly how mice detect that a peer is unconscious or in need of help. The sensory cues—such as smell, movement, or posture—that signal distress have yet to be identified. The research also does not resolve whether separate populations of oxytocin neurons control the emotional and motor aspects of the behavior, or whether the same neurons serve both functions.

The authors hope future studies will further investigate how sensory information is processed in the brain and translated into targeted actions. They also suggest that this new model of spontaneous rescue-like behavior in mice could be used to study disorders of social functioning, such as autism or depression, where empathy and prosocial behavior are often impaired.

“We aim to decode the licking-recovery link by identifying the underlying mechanisms (neural and molecular) by which social touch accelerates awakening,” Chen explained. “Besides oxytocin, which plays a dual role in rescue-like behavior (emotion and action), we want to identify additional molecules involved. We also like to explore how self-interested behaviors paradoxically foster group survival, potentially bridging the altruism-versus-self-interest debate in the evolution of empathy and prosocial behavior.”

“It is remarkable that mice are genetically programmed to engage in social licking and grooming to assist their peers, even without conscious intent. Although it remains unclear how these behaviors manifest in the wild, the observation that mice display instinctive helping behaviors suggests that rodents may have a greater capacity for prosociality than previously recognized.”

The study, “Distinct oxytocin signaling pathways synergistically mediate rescue-like behavior in mice,” was authored by Feng-Rui Zhang, Juan Liua, Jieqi Wend, Zi-Yan Zhang, Yijia Li, Eric Song, Li Hu, and Zhou-Feng Chen.