Investigating social communication and attachment deficits in prairie vole models of autism
- Awarded: 2020
- Award Type: Pilot
- Award #: 736475
Social attachments form the basis of human relationships at every level of social organization, from relationships between parents and children, romantic partners, to peers and group affiliation. However, the sensory and neural mechanisms that mediate social communication facilitating attachment are poorly understood. Prairie voles are small rodents that display social monogamy, or pair bonds, between mates. Pioneering work in voles identified the peptide hormones vasopressin and oxytocin as critical mediators of pair bonding in voles and social cognition and attachment behaviors in humans. These findings suggest that the genetics and neural control of social attachment may be conserved, and indeed, have inspired clinical trials seeking to use these hormones to ameliorate disruptions in social cognition due to neuropsychiatric conditions.
Deficits in social communication arise from disruption in the detection, processing or expression of socially relevant cues and appropriate responses. To understand the sensory pathways, neural mechanisms and genetic factors underlying social attachment, Devanand Manoli’s team has developed behavioral paradigms and in vivo imaging in voles to examine population-and ensemble-level activity in specific regions (unpublished findings). They have also developed voles with specific mutations in two autism spectrum disorder (ASD) risk genes, Shank3 and Scn2a. This work was supported in part by a SFARI Explorer award. Preliminary studies reveal deficits in social and attachment behaviors in both Shank3 and Scn2a heterozygous animals.
In the current project, Manoli’s team plans to investigate the neural circuitry underlying these observed behavioral deficits. Furthermore, they plan to determine if targeted rescue of the expression of Shank3 or Scn2a in specific regions using CRISPR-mediated activation (CRISPRa) can ameliorate these deficits.
These experiments are expected to demonstrate the central role of social communication in attachment, illuminate the ways that sensory pathways may be modulated to facilitate social attachment behaviors, and inform targeted interventions to improve social communication deficits in ASD.