Georgia State University scientists have created gene-edited hamsters for
studies of social neuroscience and have found that the biology behind social
behavior may be more complex than previously thought.
A team of Georgia State University researchers led by Regents' Professor of
Neuroscience H. Elliott Albers and Distinguished University Professor Kim
Huhman used CRISPR-Cas9 technology to eliminate the actions of a
neurochemical signaling pathway that plays a critical role in regulating
social behaviors in mammals. Vasopressin and the receptor that it acts on
called Avpr1a regulates social phenomena ranging from pair bonding,
cooperation, and social communication to dominance and aggression. The new
study, published in the Proceedings of the National Academy of Sciences
(PNAS), finds that knocking out the Avpr1a receptor in hamsters, and thus
effectively eliminating vasopressin's action on it, dramatically altered the
expression of social behavior in unexpected ways.
"We were really surprised at the results," Albers said. "We anticipated that
if we eliminated vasopressin activity, we would reduce both aggression and
social communication. But the opposite happened."
Instead, the hamsters without the receptor showed much higher levels of
social communication behavior than did their counterparts with intact
receptors. Even more interesting, the typical sex differences observed in
aggressiveness were eliminated with both male and female hamsters displaying
high levels of aggression towards other same-sex individuals.
"This suggests a startling conclusion," Albers said. "Even though we know
that vasopressin increases social behaviors by acting within a number of
brain regions, it is possible that the more global effects of the Avpr1a
receptor are inhibitory.
"We don't understand this system as well as we thought we did. The
counterintuitive findings tell us we need to start thinking about the
actions of these receptors across entire circuits of the brain and not just
in specific brain regions."
The hamsters used in the research were Syrian hamsters, which have become
increasingly important for studies of social behavior, aggression and
communication. They are the species in which vasopressin was first
demonstrated to influence sociality. Hamsters provide a powerful model for
the studies of social behavior because their social organization is far more
similar to humans than that observed in mice, even though mice are the most
common laboratory animal used. Hamsters are unique research animals in other
ways as well, explained Huhman, who is Associate Director of the
Neuroscience Institute at Georgia State.
"Their stress response is more like that of humans than it is other rodents.
They release the stress hormone cortisol, just as humans do. They also get
many of the cancers that humans get," she said. "Their susceptibility to the
SARS-CoV-2 virus that causes COVID-19 makes them the rodent species of
choice because they are vulnerable to it just as we are."
The work using CRISPR in hamsters was a significant step forward, say both
researchers. "Developing gene-edited hamsters was not easy," Albers said.
"But it is important to understand the neurocircuitry involved in human
social behavior and our model has translational relevance for human health.
Understanding the role of vasopressin in behavior is necessary to help
identify potential new and more effective treatment strategies for a diverse
group of neuropsychiatric disorders ranging from autism to depression."
Reference:
Jack H. Taylor, James C. Walton, et, al. CRISPR-Cas9 editing of the
arginine–vasopressin V1a receptor produces paradoxical changes in social
behavior in Syrian hamsters. Proceedings of the National Academy of Sciences,
2022; 119 (19)
DOI: 10.1073/pnas.2121037119