New methods for modifying genes shed light on how hormones affect animal and human social behavior
Scientists at Georgia State University produced gene-edited hamsters for social neuroscience research and discovered that the biology driving social behavior is more complex than previously imagined.
Researchers at Georgia State University lead by Regents’ Professor of Neuroscience H. Elliott Albers and Distinguished University Professor Kim Huhman used CRISPR-Cas9 technology to reduce the functions of a neurochemical signaling pathway that is crucial in controlling social behaviors in mammals.
Vasopressin and the Avpr1a receptor on which it activates influence a variety of social behaviors, including pair bonding, collaboration, and social communication, as well as dominance and aggression.
The findings of a new study published in the Proceedings of the National Academy of Sciences (PNAS) show that in hamsters, knocking out the Avpr1a receptor and therefore effectively eliminating vasopressin’s activity on it changed the expression of social behavior in unexpected ways.
“We were really surprised at the results,” says Albers. “We anticipated that if we eliminated vasopressin activity, we would reduce both aggression and social communication. But the opposite happened.”
Instead, hamsters without the receptor exhibited significantly more social communication activity than those with complete receptors. Even more intriguing, traditionally female differences in aggressiveness were erased, with both male and female hamsters expressing high levels of antagonism toward other same-sex individuals.
“This suggests a startling conclusion,” adds Albers. “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.”
Syrian hamsters, which have become increasingly relevant for studies of social behavior, aggression, and communication, were employed in the study. They were the first species in which vasopressin was shown to alter social behavior. Even though mice are the most commonly used laboratory animal, hamsters provide an useful model for studying social behavior because their social organization is significantly more akin to that of humans than that of mice. Huhman, Associate Director of Georgia State’s Neuroscience Institute, said that hamsters are also unusual research animals in other respects.
“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 says. “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.”
Both researchers agree that utilizing CRISPR in hamsters was a significant step forward.
“Developing gene-edited hamsters was not easy,” says Albers. “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.”
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