Resting state default mode network connectivity and social dysfunction in dopamine d2 autoreceptor knockout mice

Resting-state brain activity has become an important window into the neural circuits underlying psychiatric symptoms, including social dysfunction. In humans, connectivity within large-scale brain networks has been repeatedly linked to social cognition and impairment. However, understanding the mechanisms behind these associations requires translational models in which brain circuits can be studied more directly.

In this project, we developed a method to identify a translationally relevant resting state in freely moving mice, allowing us to study resting-state networks in a way that more closely parallels human research. We then applied this method to mice lacking the dopamine D2 autoreceptor, which normally helps regulate dopamine release. These mice display increased sociability, allowing us to ask whether a gene linked to human social dysfunction also changes resting-state brain networks in a mouse model with a relevant social phenotype.

We found that mice lacking the D2 autoreceptor, did not show altered local brain activity during rest, but rather communication between regions. These mice showed weaker coordination between higher-order processing and sensory regions, reduced striatal influence over the anterior cingulate cortex—a key default mode network region implicated in social cognition—and enhanced communication between the cingulate and orbitofrontal cortices. These findings suggest that dopamine may influence social behavior by shaping coordination between brain regions during rest.

Overall, this work provides a framework for studying how dopamine and other biological factors shape brain networks. This could support direct mechanistic research into social dysfunction and guide the development of biologically informed strategies for psychiatric interventions.