Mesocorticolimbic dopamine circuitry in mouse models of autism

  • Awarded: 2011
  • Award Type: Research
  • Award #: 205421

One of the core symptoms of autism spectrum disorders is impaired social interactions. One reason for this may be that individuals with autism do not experience the typical rewarding aspects of social interactions. There are specific brain areas that are critical for experiencing normal pleasures and specific chemicals in the brain that are thought to be important for promoting social interactions.

In this project, Robert Malenka and his colleagues used sophisticated techniques to study the brain’s reward circuitry and made several discoveries that may help explain the impaired social interactions of individuals with autism spectrum disorders.

First, the researchers found that the brain’s reward circuitry is much more complex than previously thought and contains different microcircuits, some of which are critical for reward but others that are critical for mediating aversion1.

Second, they examined whether the actions of the neuropeptide oxytocin in the brain’s reward circuitry are important for mediating the pleasurable aspects of social interactions. This topic was of particular interest because oxytocin is being tested as a possible therapeutic agent in the treatment of autism. The results from the current study show that oxytocin’s action in a key node of the reward circuitry — called the nucleus accumbens — is critical for social reward and that oxytocin works in a coordinated fashion with another important chemical messenger, serotonin2.

Finally, Malenka and his team characterized the behavioral and circuit abnormalities in a mouse model of a prominent genetic cause of autism called 16p11.2 deletion syndrome. They found that the basal ganglia, a key region of the brain, do not function properly in these mice and that this may account for several of the behavioral abnormalities observed in these animals3.



1.Lammel S. et al. Nature 491, 212-217 (2012) PubMed
2.Dölen G. et al. Nature 501, 179-184 (2013) PubMed
3.Portmann T. et al. Cell Rep. 7, 1077-1092 (2014) PubMed
Subscribe to our newsletter and receive SFARI funding announcements and news