Using mice to research social interaction and reward processing  in autism, and potential medication

There is a theory that some autistic people have differences in the brain’s social reward system when compared to non-autistic people. For this subgroup of autistic people, medication to address those differences could be beneficial, for example in alleviating social anxiety, decreasing social difficulties and potentially improving quality of life. Additionally, since we learn a lot from other people in social situations, autistic children may miss out on important learning if they are not attending enough to social situations. 

‘Mouse models’ of autism

The AIMS-2-TRIALS team led by Peter Scheiffele at the University of Basel is using mouse models to explore these ideas. In some ways, human and mice brains are quite alike. This is not so much the case for the sensory systems because mice use mostly their whiskers and smell whereas humans are very visual, but the ways that human and mice brains process positive experiences, including social information, are quite similar.

In this research, mice were bred without a protein in their brains that controls the organisation of neuronal connections. The loss of this protein in cells of the reward system of mice modified how these cells respond to the hormone oxytocin. The cells that would usually activate in response to social contact no longer did so, and these mice behaved less socially than those without the special breeding. Researchers then tested a new pharmacological intervention – what could eventually become a medication for humans – and were able to restore the responses to oxytocin.  They then put these mice in social situations and found that the activation of the appropriate brain cells was also restored and the mice’s social behaviour was more typical.

Developing treatments

This is exciting research because it is possible that the successful ‘medication’ could be adapted for use with humans. Similar compounds have already been safety tested in the field of cancer treatment and are promising because they have very specific, selective effects. It will be important to explore how long any changes caused by medication might last. It may be that medication is more beneficial – or long-lasting – if administered at critical periods during development. It will also be vital to check for side effects and to continue to explore ways of identifying those who might benefit from the medication.

Translating back from mice to people

Further research will need to determine whether the general principles demonstrated in these mouse studies transfer to humans. Related findings have already been described by researchers such as Webb et al. (2010), who found that toddlers with more severe symptoms of autism appeared to become familiar with faces more slowly than comparison groups. As with the mice, this was only the case with faces, the same result was not found with objects. One of the researchers in that study was Emily Jones of Birkbeck College in London, who is now part of the AIMS-2-TRIALS consortium. In a 2017 paper, Emily’s team suggests that early parent-led interventions for social attention might have the potential to improve developmental achievements for children with a high likelihood of autism diagnosis. This study shows the potential for not just medicine but also non-medical interventions to have an impact on brain systems underpinning social attention, to improve quality of life, and potentially even developmental achievements.

References

Hörnberg, H., Perez-Garci, E.,  Schreiner, D., Hattstatt-Burkle, L., Magara, F., Baudouin, S., Matter, A., Nacro, K., Pecho-Vrieseling, E., and Scheiffele P. (2020) Restoration of oxytocin receptor signaling and social recognition in a mouse model of autism.

Jones EJH, Dawson G, Kelly J, Estes A, Webb SJ. Parent-delivered early intervention in infants at risk for ASD: Effects on electrophysiological and habituation measures of social attention. Autism Res. 2017;10(5):961–972. doi:10.1002/aur.1754

Webb, Sara Jane & Jones, Emily & Merkle, Kristen & Namkung, Jessica & Toth, Karen & Greenson, Jessica & Murias, Michael & Dawson, Geraldine. (2010). Toddlers with Elevated Autism Symptoms Show Slowed Habituation to Faces. Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence. 16. 255-78.

Principal investigator:

Peter Scheiffele, University of Basel