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GABAergic Interneurons in Cognition: Gender Disparities
Elizabeth Powell, Ph.D.
School of Medicine, University of Maryland, Baltimore
The long-term goal of this research project is to develop a methodology to test cognitive deficits using an animal model. Patients with frontal lobe epilepsy, autism, and schizophrenia exhibit loss of attention, planning, and normal social behavior. The medial frontal cortex (MFC) is strongly implicated in attention tasks, and the orbital frontal cortex (OFC) mediates social behavior, judgement, and goal neglect. While developing a behavioral task to assess frontal lobe cognition in mice, we have discovered a dramatic gender disparity. In a pilot study, female littermates required more than twice the number of trials and up to four-fold more time to reach criterion. This data supports numerous studies in humans demonstrating gender differences in frontal lobe mediated task. My past research has uncovered a transgenic mouse, lacking the urokinase plasminogen activator receptor gene (uPAR-/-), that exhibits decreased GABAergic interneurons in the frontal cortex. The uPAR-/- mouse has intact learning and memory function, but displays abnormal emotional and social behavior. Thus the uPAR-/- mouse is a good rodent to test the hypothesis that GABA mediates frontal lobe cognition. This proposal will test the hypothesis that frontal lobe disruptions in GABA differentially modulate attentional and motivational behaviors.
