Understanding the neurobiology of attachment deficits in ASD

  • Awarded: 2017
  • Award Type: Explorer
  • Award #: 548009

Social attachment plays a central role in most, if not all, levels of human interaction and is critically affected in conditions such as autism spectrum disorders (ASD), which manifest with a dramatic disruption of interpersonal interactions early in life. Pioneering research in prairie voles (Microtus ochrogaster), which display social attachment behaviors such as enduring pair bonds between mates, social monogamy and biparental care, identified vasopressin (AVP) and oxytocin (OXT) as critical mediators of pair bonding. Strikingly, AVP and OXT pathways have also been implicated in social behaviors in humans. Thus, findings in prairie voles may help inform our understanding of attachment behaviors in humans.

While the pathways regulated by AVP and OXT signaling appear to specify the circuits underlying attachment behaviors in humans and other mammals, the way other genes within these circuits influence specific aspects of attachment behaviors remains unknown. Thus, distinct behavioral endophenotypes may arise as a consequence of disruptions to subsets of these genetic and neural pathways as a consequence of mutations in genes that function in particular regions of these circuits. Recent studies have identified mutations in patients with ASD and identified genes in which mutations are highly correlated with disease occurrence. However, the relationship between behavioral and biological modules and endophenotypes, and distinct mechanisms that contribute to the diverse symptoms that comprise these syndromes, remains unclear.

Devanand Manoli and colleagues have developed techniques to render prairie voles amenable to molecular genetic approaches and dissect the neural basis of social attachment. We are, therefore, for the first time, well poised to understand how specific genes and biological pathways function in the circuits underlying social attachment and contribute to distinct aspects of attachment and other behavioral processes. They propose to use prairie voles to understand the neurogenetic and molecular basis for social attachment. Manoli’s team will 1) generate voles with targeted mutations in SCN2a, which has been highly correlated with ASD and 2) functionally manipulate neurons expressing the oxytocin receptor (OXTR) to determine if modulation of their activity can ameliorate deficits in attachment behaviors resulting from loss of SCN2a function.

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