Defining Prenatal Alcohol Exposure Impact on Frontoparietal Signaling During Cognitive Control

About This Grant

Project Summary: Consumption of alcohol during pregnancy results in the development of fetal alcohol spectrum disorders (FASD), which is conservatively estimated to affect 5% of United States first graders. Individuals with FASD often report difficulties with executive function domains including cognitive control, which is the ability to maintain goal-directed behavior despite distractions. Such cognitive control deficits have been replicated in mouse models of prenatal alcohol exposure (PAE); however, the electrophysiological underpinnings of these deficits are not understood. To fill this knowledge gap, I propose to investigate the underlying electrophysiological mechanism(s) of PAE-associated cognitive control deficits by combining translational touchscreen testing and in vivo electrophysiology with a first- and second-trimester equivalent moderate PAE paradigm. My central hypothesis is that PAE induces long-term impairments in cognitive control by reducing parvalbumin fast-spiking interneurons in the posterior parietal cortex (PPC), which results in an inability to gate incoming excitatory signaling in frontoparietal circuits required to exert cognitive control. Electrodes will be implanted into the PPC and medial prefrontal cortex (mPFC), allowing data collection during the 5 Choice Continuous Performance Task (5C-CPT). 5C-CPT is a translational touchscreen paradigm that assesses many domains of executive function, including cognitive control. Multiple analytic tools will be used to investigate the impact of PAE on the excitatory/inhibitory balance and oscillatory signaling of the PPC. Additional tools will be used to determine if PAE dysregulates frontoparietal signaling via decreases in synchronous activity between the mPFC and PPC. Collectively, this proposal will determine the impact of PAE on electrophysiological functions in both the PPC alone and the mPFC-PPC reciprocal circuitry during trials taxing cognitive control. The successful completion of this proposal will provide crucial information on the lasting neurological impacts of moderate PAE on individual neurons and oscillations in both the PPC and the reciprocal mPFC-PPC circuitry. Additionally, this work will provide intensive training in awake-behaving high-yield electrophysiology, translational touchscreen behavior, and complex data analysis.