Oxytocin Neurons May Help Mice Recognise When Danger Has Passed

Oxytocin is widely associated with love, trust, and bonding. Now, researchers have found evidence that brain cells responsive to the so-called "love hormone" could also help us recognise when a threat is over.

Oxytocin has long been viewed as more than a simple social chemical. Its effects may vary with the circumstances, an individual's emotional condition, and whether they regard someone else as safe or as a threat.

Research in mice has identified a small population of neurons that express oxytocin receptors and seem to affect both social approach and fear extinction – the learned understanding that something once linked with danger has become safe.

Published in Brain, the study identifies the paraventricular thalamus (PVT) as a potential point of convergence for social behaviour and fear. The results may offer an early indication of why both functions can be impaired in conditions including autism and anxiety disorders.

Oxytocin-sensitive neurons in the paraventricular thalamus

To investigate oxytocin's differing effects, researchers in Japan examined oxytocin-responsive neurons in the PVT, a brain area implicated in stress, motivation, and emotional behaviour.

The scientists used genetically modified male mice and selectively silenced or activated these neurons to determine their effects on social behaviour and fear extinction.

Silencing the neurons made the mice less inclined to engage with unfamiliar animals. This lower level of social interaction appeared in two separate social-behaviour tests, and could not be explained by reduced movement or heightened anxiety.

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Yet activating these same neurons did not make the animals more sociable. This implies that, although the cells may be required for typical social behaviour, simply switching them on does not itself boost social interest.

Fear extinction after danger has passed

The team next investigated fear extinction.

The mice were initially trained to connect a specific environment with a mild electric shock. Afterwards, they were repeatedly placed back in that environment without another shock being delivered.

Silencing the oxytocin-responsive neurons did not stop the animals forming the initial fear memory. But when they returned to the setting that was now safe, the mice continued to freeze – staying still as an expression of fear. This indicated that they struggled to learn that the threat had ended.

Neuron activation led to another outcome. During the initial phase of fear-extinction learning, the mice froze less, although this effect was absent when they were assessed the next day and again one week later.

In contrast, altering comparable oxytocin-responsive neurons in other brain regions did not change the mice's sociability. This suggests that these cells' role in social behaviour is dependent on their location.

This regional variation is important, since oxytocin does not generate an identical social response in every neural circuit. A 2024 review published in Hormones and Behavior, which drew on research in California mice, likewise concluded that oxytocin may encourage either social approach or social avoidance according to the context and the brain circuits involved.

(PixelsEffect/Canva)

Early clues from human data

The researchers also sought evidence that oxytocin and the thalamus could be connected with social traits in people.

They examined information from 30 Japanese adolescents: 19 had been diagnosed with autism spectrum disorder, while 11 participants were developing typically. Salivary oxytocin concentrations were compared with thalamus measurements from MRI scans and evaluations of autism-related traits.

The team identified associations among oxytocin levels, thalamic characteristics, and certain behavioural measures. However, the analysis was small and exploratory, while oxytocin in saliva may not represent the hormone's activity within the brain.

The animal research has significant limitations as well. The study chiefly involved male mice, and artificial activation of the selected oxytocin receptor-bearing neuron population does not mimic the brain's natural release of this hormone.

Consequently, these results do not yet establish that naturally released oxytocin directly governs social behaviour or fear extinction.

Related: Brain Mechanism That Regulates Fear Discovered in Mice, Scientists Say

Should later research verify a comparable system in humans, it may help scientists understand conditions involving problems with social behaviour or fear regulation, including autism and anxiety disorders, more clearly.

At present, the findings indicate that oxytocin's effects depend closely on exactly where and when it acts in the brain – potentially influencing both social approach and the capacity to recognise that danger has passed.

The study appeared in Brain.

This article was fact-checked by Michael Irving and edited by Michael Irving. Although we take pride in our process, we are only human. If you notice an error, please let us know.