Abstract

Identifying and diagnosing age-related dementias prior to the onset of significant degeneration is a major challenge to developing effective interventions. Many of the earliest signs of dementia, particularly frontotemporal dementia (FTD), are increasingly recognized as changes in social behavior and psychiatric symptoms. New models that display the earliest circuit and behavioral disruptions associated with FTD are necessary. Our lab has generated a novel model system for studying social attachment disruptions in FTD and other age-related diseases, in a species that shows enduring social bonds: the prairie vole. The rich repertoire of prairie vole social behaviors bears a strong resemblance to displays of social attachment in humans and may engage similar, conserved brain processes. We have used advanced genetic approaches to introduce mutations in genes that are highly linked to FTD and find that these mutations disrupt bonding behaviors in voles, as they do in humans. This project aims to map the trajectory of social behavior through adulthood and late age and identify the underlying neural and molecular signatures that predict both resilience with age and vulnerability to disease. This is the first genetic animal model to replicate the social attachment impairments seen in patients, offering a powerful platform for targeting the neural mechanisms affected earliest in dementia.