Disruptions in social attachment and cognition occur in the context of autism spectrum disorder (ASD). However, the neural mechanisms that mediate social communication and complex social behaviors that facilitate attachment are poorly understood. Mice and other traditional genetic model organisms do not exhibit enduring social attachments, precluding genetic analysis of these important behaviors.

Prairie voles display social monogamy, or pair bonds, between mates and engage in a rich repertoire of social behaviors that strikingly mirror complex social behaviors in humans. With funding from a SFARI Explorer Award, the Devanand Manoli lab generated prairie voles bearing mutations in genes strongly associated with ASD, Scn2a and Shank3. These studies lay the groundwork for investigating how mutations associated with ASD disrupt the neural processing mediating social interactions and bonding. Manoli and colleagues have already identified deficits in pair bonding as well as altered patterns of vocal communication or sensory processing in these mutants, funded by a SFARI Pilot Award. Here, they will implement microendoscopic calcium imaging of neural activity and single-nucleus RNA-sequencing in three brain regions (medial amygdala, paraventricular nucleus of the hypothalamus, and anterior cingulate cortex) implicated in social and attachment behaviors. These studies will allow them to determine whether mutations in different genes associated with ASD implicate distinct or convergent circuits or molecular pathways to alter behavior, or whether specific mutations have effects that differ between neural populations implicated in separable phenotypes.