Mapping functional neural circuits that mediate social behaviors in autism

Deficits in social behaviors are a core aspect of autism and can be quite debilitating. Despite significant advances in identifying genes associated with autism spectrum disorders, the neural circuits that mediate social behaviors remain obscure.

Fan Wang, Richard Mooney and their colleagues at Duke University Medical Center in Durham, North Carolina, are developing a new approach to systematically mapping the neuronal ensembles in the mouse brain that are active during specific social interactions. The researchers have developed a mouse line that transiently and selectively expresses a foreign receptor in activated neurons, along with viruses that infect only neurons expressing the foreign receptor immediately after execution of a specific behavior. This way, timed injection of the designer virus into the mouse’s brain allows the investigators to selectively infect and permanently label neuronal ensembles activated by a specific social encounter.

Among the vast and complex neural networks involved in social behaviors are key circuits that include the prefrontal cortex (PFC), extended amygdala (Amy), hypothalamus (HTh) and other limbic structures. Wang’s group plans to label mouse neurons that are transiently activated during selected social and communication behaviors along the PFC-Amy-HTh axis, trace their axonal projections, and establish a detailed functional connectivity diagram. The researchers plan to map the circuitry in both normal mice and autism model mice.

This technology may have broad applications for studies of autism and other mental disorders. The functional wiring diagram of social circuitry may provide an important framework for subsequent studies that aim to understand how components within the circuits mediate specific aspects of social behavior, and how dysfunction of these circuits could lead to autism symptoms.