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. We complement our approaches with 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 recently generated the EAAT3glo/CMKII mice, a novel mouse model with EAAT3 ovexpression in forebrain as a novel animal model for OCD research. As detailed in (Delgado-Acevedo et al, 2018), EAAT3glo/CMKII mice displays increased anxiety-like and compulsive-like behaviors, deficits in in long-term extinction of fear memory. More recently, we demonstrated that EAAT3glo/CMKII mice also exhibits grooming syntax alterations, as well as alterations in dopaminergic neurotransmission, which involved in compulsive behaviors (Escobar et al, 2021). Our ongoing efforts in this OCD mouse model are towards additional tests of compulsivity and impulsivity, as well as other behavioral domains like depression-like behavior and executive functions. We also continue our classic studies in the 5-HT transporter (SERT) KO mouse, a long well-established animal model of anxiety-like behavior and prone to develop depressive-like behaviors. Current aims include a) the elucidation of neural dynamics alterations by using chronic, multi-electrode implants in behaving SERT KO mice; b) how SERT can moderate the benefical impact of voluntary physical activity on cognitive performance, and c) determining specific synaptic alterations in the excitatory-inhibitory balance in cortex and hippocampus, to substantiate some of thealtered phenotypes seen in SERT KO mice.