How do people and animals remember each other? Social memory, or the ability to recognize and remember other individuals, is the foundation of social life across animals. But the biology of how social memories are formed and maintained has remained a mystery for scientists.
Now, new discoveries in rats and mice suggest that the animals maintain their memories of each other because of a molecular pathway centered on the "love hormone" oxytocin. The experiments were published in the February 1 issue of Science Signaling.
The results suggest that this mechanism might go awry in social disorders such as autism and schizophrenia, although more research is needed. The authors of the study believe their findings could also inform scientific efforts to treat autism with therapies based on oxytocin.
Social memory: the foundation for how we interact
Social memory is one of the basic building blocks of socialization and serves as the basis of social structures ranging from small bands of mammals to human civilizations. It allows individuals to distinguish friends from strangers and adjust their behavior accordingly, whether that be through aggression, cooperation, or even mating.
"Gregarious animals living in societies utilize social memory to remember and recognize different individuals," said Yun Wang, a principal investigator at Peking University in Beijing, China and senior author of the new study.
"Let's say we're at a party," she explained further. "It is natural that we can identify friends to greet with a hug or to introduce [ourselves] to someone we know we have not met before."
People depend on their social memories to exhibit appropriate social behaviors. This has led some researchers to suspect that problems with social memory might contribute to disorders that cause abnormal social behavior, such as autism spectrum disorder and schizophrenia, according to the study.
Scientists also know that the hormone oxytocin and its receptor are highly active in areas of the brain that control social behavior and emotion. Oxytocin is commonly referred to as the "love" or "cuddle" hormone because of its important role in social bonding and arousal.
On the biological level, however, things remain less clear. The mechanisms behind social memory are still vague and can vary across different regions of the brain, according to Wang. Researchers are also unsure about the role of oxytocin and its receptor in maintaining social memories.
Distinguishing friends from strangers in rodents
A research team led by Fei Wang, a researcher at Peking University and lead author of the new study, and senior author Wang decided to define the link between oxytocin and social memory, as well as any other signaling molecules that might play a role.
The team started by focusing on the oxytocin receptor and an enzyme called PKD1, which participates in several processes in the nervous system. As they studied human kidney cells in culture, the authors discovered that PKD1 altered the oxytocin receptor through a biochemical reaction.
They then moved to animal studies and examined social behavior and memory in rats and mice. In these experiments, the team tested the animals' social memory by seeing whether a given rodent could tell apart other rodents that it had recently played with.
Using CRISPR gene editing, Wang's team also created a line of rats that carried a mutation in the oxytocin receptor, which prevented the receptor from being modified as usual by PKD1.
The scientists observed that social interactions caused PKD1 to alter the oxytocin receptor in a positive feedback loop, which in turn raised levels of the receptor and triggered further oxytocin activity. This self-sustaining mechanism was absent in the rats that had the mutated oxytocin receptor.
Both the regular rats and the gene-modified rats behaved similarly during tests of short-term social memory. For example, both groups of rats preferred to interact with juveniles that they hadn't previously met than with ones they had met but been separated from for 30 minutes.
However, the rats with the modified receptor showed no preferences after being separated for 24 hours, and seemed to treat both novel and familiar juveniles as strangers. The researchers observed a similar lack of long-term social memory in mice when they deactivated PKD1 with a virus.
"In a word, the ability to meet a new friend, transform the episodic information into memory, and store it for a long time could be partially regulated by the status of [oxytocin receptor]," Yun Wang said. "Our results provide brain area- and cellular signaling-specific evidence for social memory consolidation."
The team's discoveries about the oxytocin receptor could inform ongoing efforts to treat autism spectrum disorder and other social disorders, she added. For example, the effects of PKD1 should be considered when trying to use oxytocin treatments for patients with autism, which have so far yielded mixed results in clinical trials.
"These findings may be helpful in identifying more efficient therapeutic strategies to [modulate] the [oxytocin] system and to improve social learning and prosocial behaviors," the team speculated.