CONNELLY LAB
CONNELLY LAB
RESEARCH
How do your genes shape the way your brain works?
How does this affect the way you interact with the world?
To dissect the complex phenotypes of genes, brains, and behavior, we study the prairie vole model system and the oxytocin gene regulation system!
Why do we look at prairie voles?
Like humans, prairie voles are exquisitely sensitive to their environments and exhibit complex social behaviors. From exhibiting human-like social monogamy, to raising offspring with heavy involvement from both parents, the prairie vole is the ideal rodent model to identify how genes, brains, and behaviors develop within social contexts.
In collaboration with Sue Carter and Karen Bales, we initially characterized the oxytocin gene in the prairie vole to allow us to study how it is epigenetically modified based on early life environments. Just like in humans, early life experience plays an important role in modulating the oxytocinergic system which registers and responds to early life events like parenting. These changes correspond to coordinate changes in gene and protein expression early in life, leading to changes in social behavior as adults.
Building on our early work, the Connelly Lab now explores several facets of oxytocin gene regulation and the development of social behavior in the prairie vole system.
Why do we look at oxtr epigenetics?
Oxytocin is a neuropeptide that has been implicated in the development and expression of social behavior. Oxytocin modulates various behaviors through its association with its single known receptor, OXTR, which shows remarkable variation in distribution and density across and within species.
In humans, OXTR contains a methylation-specific regulatory region (MT2 region) within its promoter. Our lab has found that human and vole OXTR is homologous, including the MT2 regulatory region. Additionally, we have shown that increases in MT2 DNA methylation leads to decreased gene expression in both human and prairie vole brains, and that saliva can be used as a biomarker for brain methylation and transcription state.
Previous studies from our lab and others indicate that altered levels of DNA
methylation in OXTR are a risk factor for several psychiatric disorders, including
autism spectrum disorder, postpartum depression, schizophrenia, major
depressive disorder, anorexia nervosa, and psychopathy. The factors that regulate
the expression of the oxytocin receptor, rather than oxytocin itself, may provide
an improved explanation for the variability in social behavior displayed both
within and between species
What other avenues are we exploring in the lab now?
Alternative oxtr transcripts
Father's care on offspring
Maternal brain
Microglia's role in social behavior
Postpartum Depression