Laura N. Smith, PhD

Education and Training

• George Mason University, PhD, Department of Psychology, 2008
• Harvard Medical School, Postdoctoral Fellow/Instructor, Department of Psychiatry
• University of Texas Southwestern Medical Center, Postdoctoral Fellow, Department of Psychiatry

Research Interests

• Broadly, I am interested in the underlying molecular and circuit mechanisms of complex behavior, particularly in how alterations in such pathways lead to the maladaptive features of mental illnesses. We know that several neuropsychiatric illnesses show evidence of altered synaptic function, which affects the ability of neurons to communicate properly. For instance, ineffective synaptic pruning is observed in autism spectrum disorders and may contribute to symptoms such as sensory hypersensitivity, social overstimulation and epilepsy. Repeated exposure to drugs of abuse is also associated with long-lasting synaptic alterations in brain reward regions, and emerging evidence suggests that addiction-related synaptic and behavioral changes, similar to learning and memory, require the synthesis, or translation, of proteins in their local vicinity. Together these findings suggest that addiction is promoted and sustained through the coercion of normal plasticity mechanisms. Thus, investigating the function of developmental proteins in the adult brain, with regard to psychiatric and substance-related disorders, may reveal novel therapeutic and preventative strategies.
• One major project in my lab examines how pathways capable of affecting synaptic remodeling are involved in the brain changes associated with, and that may sustain, addiction-related behaviors. Our current work focuses on the fragile X messenger ribonucleoprotein, or FMRP, a key regulator of local protein translation. Our lab has shown evidence that both FMRP and its target, the activity-regulated cytoskeleton-associated protein (ARC), are critically involved in hedonic shifts in intravenous drug taking. At the same time, FMRP appears to limit cocaine's structural and functional effects on synapses in prominent reward-related brain regions-the nucleus accumbens and dorsal striatum. Ongoing studies are aimed at defining the cell type-specific roles of FMRP and its targets in addiction and reward function.
• A second major aim in my lab is to contribute to the understanding of autism spectrum disorders (ASDs), particularly regarding reward function. Given the important roles in brain plasticity that many developmental proteins play, their loss or malfunction, not surprisingly, is associated with neurodevelopmental and neuropsychiatric disorders. Loss of FMRP results in fragile X syndrome, one of the most significant identified causes of ASD. By studying drugs of abuse and other reinforcing substances and behaviors in mouse models lacking these developmental proteins, we observe how plasticity, reward and other normal processes malfunction in these diseases.
• The Smith Lab is also involved in collaborations investigating the development of non-opioid analgesics, as well as studies on the long-term impact of prenatal exposure to substances of abuse.