Summary: Using optogenetics, researchers precisely controlled oxytocin-producing neurons and found that oxytocin can amplify both friendly and aggressive social behaviors.
Source: Max Planck Institute
During pandemic lockdowns many couples experienced intensified emotions—some grew closer while others grew apart. Oxytocin, a peptide made in the brain, may help explain this duality. As a neuromodulator, oxytocin can promote social bonding in some contexts and increase aggression in others. Researchers from the Weizmann Institute of Science and the Max Planck Institute of Psychiatry studied mice living in semi-natural conditions and used optogenetics to manipulate oxytocin-producing neurons with high precision. Their findings offer important insights for potential therapeutic uses of oxytocin in conditions such as social anxiety, autism, and schizophrenia.
Most knowledge about neuromodulators like oxytocin comes from behavioral experiments in highly controlled laboratory settings. Those sterile environments limit external variables, but they may also miss crucial elements of natural social behavior. Recent work indicates that observing animals in enriched, semi-natural settings provides a deeper understanding of how neuromodulators influence real-world social interactions, which is essential when translating results to humans.
Prof. Alon Chen’s laboratory developed an experimental system that lets researchers follow groups of mice in enriched environments resembling natural living conditions. These arenas are filled with stimuli the animals can explore, and behavior is recorded continuously with cameras for computational analysis. The long-term project, ongoing for eight years, was led by researchers Sergey Anpilov and Noa Eren, together with staff scientist Dr. Yair Shemesh. The main innovation was integrating optogenetics—technology that uses light to activate or silence specific neurons—into a wireless, lightweight, head-mounted device that can be used while animals live and interact freely. Collaborating with optogenetics expert Prof. Ofer Yizhar, the team expressed a light-sensitive protein in oxytocin-producing cells in the hypothalamus. When light from the wireless device reached those neurons, their sensitivity to input from other brain circuits increased.
“Our objective,” explains Anpilov, “was to find a balance: observe behavior in a naturalistic context while retaining the ability to ask targeted neuroscientific questions.” Shemesh adds that traditional experiments often last only minutes in impoverished environments, whereas this setup allowed continuous monitoring of social dynamics across days.
Using this platform, the researchers tested the social salience hypothesis of oxytocin. Historically described as the “love hormone,” oxytocin has been linked to pro-social behaviors such as eye contact and bonding. Yet prior results have been inconsistent. The social salience hypothesis proposes that oxytocin amplifies the significance of social cues, which can lead to cooperative or antagonistic outcomes depending on personality traits and the social environment.
The team gently activated oxytocin-producing neurons in male mice and compared behavior in enriched semi-natural arenas to behavior in standard laboratory cages. In the semi-natural groups, increased oxytocin signaling initially heightened social interest but soon led to more aggressive interactions, as males competed for territory and resources. By contrast, activating oxytocin neurons in standard, minimal laboratory conditions reduced aggression. “In a naturalistic all-male social setting, competition and resource defense make aggressive responses more likely,” notes Anpilov. “In a deprived lab setting the social cues are different, producing a different effect of oxytocin.”
Oxytocin can cause antagonistic behaviour
The results demonstrate that oxytocin’s effects are context-dependent: in a rich social environment it can escalate both affiliative and agonistic behaviors, whereas in simple, non-competitive settings it can suppress aggression and enhance social tolerance. Noa Eren emphasizes the practical implications: “Oxytocin does play a role in social behaviors such as closeness and eye contact, but it does not uniformly increase sociability. Its impact depends on the surrounding social context and the individual’s characteristics.”
These findings suggest a more nuanced approach is necessary when considering oxytocin as a therapeutic agent. Researchers and clinicians should account for environmental context and individual differences when designing treatments that target social behavior. The study also highlights the importance of using complex, ecologically valid behavioral paradigms when investigating neuromodulators.
The research team included contributors from the Max Planck Institute for Psychiatry in Munich—research students Asaf Benjamin and Stoyo Karamihalev, staff scientist Dr. Julien Dine, and postdoctoral fellow Dr. Oren Forkosh—along with Prof. Shlomo Wagner and Dr. Hala Harony-Nicolas from Haifa University; Prof. Inga Neumann and Vinicius Oliveira from the University of Regensburg; and electrical engineer Avi Dagan.
About this neuroscience research article
Source: Max Planck Institute
Media Contacts:
Anke Schlee – Max Planck Institute
Image Source:
Weizmann Institute of Science
Original Research: Open access. Title: “Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors.” Authors: Sergey Anpilov, Yair Shemesh, Noa Eren, Hala Harony-Nicolas, Asaf Benjamin, Julien Dine, Vinícius E.M. Oliveira, Oren Forkosh, Stoyo Karamihalev, Rosa-Eva Hüttl, Noa Feldman, Ryan Berger, Avi Dagan, Gal Chen, Inga D. Neumann, Shlomo Wagner, Ofer Yizhar, and Alon Chen. Published in Neuron, DOI: 10.1016/j.neuron.2020.05.028
Abstract
Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors
Behavioral neuroscience increasingly uses complex phenotyping approaches that require compatible methods for manipulating neuronal activity. The authors present a compact, magnetically activated, head-mounted device that enables wireless optogenetic stimulation in group-living mice within an enriched semi-natural arena over multiple days. Using this tool, repeated activation of oxytocin neurons in male mice produced divergent effects on pro-social and agonistic behaviors depending on social context. These results support the social salience hypothesis of oxytocin and underscore the importance of environmental complexity when studying social neuromodulators. The wireless device can be adapted to many behavioral paradigms previously limited by tethered light delivery or confined testing environments.