Some Illustrations from “National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services
Our studies search for the functional, in vivo characterization of novel and previously established candidate genes in anxiety, depression, bipolar disorder and OCD. To this end, we generate rodent models using both transgenic technology and viral technology to manipulate genes in specific neuronal types and/or brain regions. We extensively characterize our rodent models by behavioral phenotyping, biochemical, pharmacological and neurochemical approaches. In addition, we have a strong collaborative network to use electrophysiological approaches to understand the impact of altered gene expression at synaptic level. One of our major targets of current interest is SLC1A1, the gene encoding the neuronal-epithelial glutamate transporter EAAT3. We have generated conditional, Cre-mediated EAAT3 KO and EAAT3 ovexpressing mice, as a plausible genetic model of OCD. We are also very interested in continuing our studies in the 5-HT transporter (SERT) KO mouse, a well-established animal model of increased anxiety-like behavior and prone to develop depressive-like behaviors. Current studies are intended to evaluate specific synaptic alterations in cortex and hippocampus, and to decipher how they can explain some of the altered phenotypes that SERT KO mice exhibit.