The CRISPR-Cas9 gene-editing technique can be used to change genetic coding with great precision, and its uses include curing disease and fixing genetic faults. Now it's been used to change animal behavior – and the results are not what scientists were expecting.
CRISPR was used on a group of hamsters to knock out the Avpr1a receptor, which is acted on by the hormone vasopressin. Vasopressin is linked to social actions, such as bonding, cooperation, communication, dominance, and aggression.
Without the Avpr1a receptor, the team behind the study expected social communication and aggressive behavior to be reduced.
Instead,
the opposite happened: the hamsters without the receptor showed much
higher levels of social communication and aggression. Typical sex
differences in aggressiveness disappeared as well, with hamsters of both
sexes displaying high levels of aggression towards other same-sex
individuals.
"This suggests a startling conclusion," says neuroscientist H. Elliott Albers from Georgia State University.
"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."
Hamsters
are sometimes used as stand-ins for humans in experiments because their
social organization is somewhat similar to ours. Here, Syrian hamsters (Mesocricetus auratus) were used – the species in which vasopressin was first shown to have an influence on sociality. Their stress response is similar to
humans too – they produce the hormone cortisol when stressed, just like
we do.
This
means that the surprising results outlined in this research could
potentially apply to human beings. It could give scientists a better
idea of how genes interact with neural circuits in our brain to control
how we treat other people.
"We don't understand this system as well as we thought we did," says Albers.
"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."
Flank
marking – a scent-marking behavior used by many rodents – was one of
the behaviors altered in the hamsters given the CRISPR treatment,
leaving their scent on the environment in order to assert dominance and a
choice of mate.
While
flank marking isn't something that humans do, variations in other types
of social behavior are key indicators when it comes to neural
conditions – think about the fear of social interaction in some people
with anxiety, for example. The scientists are hopeful that their work
could potentially shed some more light on these conditions and their
treatments.
The
study also gives us another example of just how well developed CRISPR
editing has now become, and the significant difference these edits can
make. The team expects to see future studies in hamsters looking at the
same receptor.
"It
is important to understand the neurocircuitry involved in human social
behavior and our model has translational relevance for human health," says Albers.
"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."
The research has been published in PNAS.