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Our focus is on the prenatal effects of environmental agents and protons on offspring neurodevelopment and behavior. We also study Lphn3, a gene linked to ADHD. The LPHN3 protein is highly expressed in several brain regions but its function is poorly understood. Using CRISPR/Cas9 we deleted exon 3 to create a constitutive knock-out line of rats. These rats are hyperactivity and have cognitive deficits. We then created an Lphn3 floxed line that we are crossing to TH-Cre rats to create a catecholamine-specific conditional knock-out. This line will be used to test the role dopamine and norepinephrine. In collaboration with Dr. Ashley Ross, we're using fast scan cyclic voltammetry to assess dopamine signaling in these genetic models.
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My research interest is in the area of developmental impacts, including genetic, environmental, and stress-related factors, on cognitive ability and behavioral sequelae throughout the lifetime. Particular interests are in developmental manganese. Using CRISPR/Cas9, we developed a floxed Slc30A10 line that we are crossing to TH-Cre rats to understand how Mn is regulated in cells in the presence of excel Mn. The Slc30A10 protein is a intracellular Mn exporter. We hypothesize that as Mn accumulates during chronic Mn exposure, it slowly reaches intracellular concentrations that inhibit the exporter causing Mn to become trapped in the cell leading eventually to neurotoxicity.
I conduct tests with rats and mice for lab projects in the Animal Behavior Core. One project I work on is assessing the neurotoxicity of a commonly used insecticide (deltamethrin) in young and adult rats. I also test mice for other labs that investigators hypothesize may have effects on behavior.
My research is on understanding what LPHN3 does in the brain. I’m using two rat models as tools to investigate this understudied gene and protein. One is a constitutive knock-out (K) of Lphn3 and the other a conditional KO only in TH-positive cells. The KO leads to hyperactivity and severe cognitive deficits in striatally mediated egocentric and hippocampally mediated allocentric learning and memory. These rats also show abnormal striatal tonic dopamine release, both in quantal size and frequency by fast scan cyclic voltammetry with Dr. Ashley Ross in Chemistry. I plan to compare the constitutive to the conditional Lphn3 KO rats to separate the role of catecholamines from other cell types expressing LPHN3 since it is also expressed in glutamatergic neurons.
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