Enduring Impact

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We now know that neurotransmitters that we have studied for decades as signaling molecules at adult synapses also play important roles in brain development. To gain traction with this question, we are examining the role that synaptic transporters play in sculpting structural and functional aspects of brain development using both genetically modified mice as well as behavioral manipulations in juvenile animals. For example, we ask whether mutations in transporter genes that impact risk for lifelong mental illnesses produce their effects in the embryo, in juvenile animals or in adults, focusing on biochemical, cellular, physiological and behavioral changes. Key disorders of interest are those linked to perturbations in dopamine, serotonin, acetylcholine and glutamate signaling (e.g. ADHD, addiction, autism, schizophrenia, and dystonia). Secondly, we seek to understand how early-life stress leads to long-term changes in behavior that mimics that seen in humans with depression and anxiety disorders and whether these changes reflect alterations in neurotransmitter transporter function and regulation. Finally, we seek to combine our observations from the two areas noted above to understand the intersection of genes and environment in determining disease risk.