It is easy to think of examples of how stressful life events can impair cognition. Of interest to the principal investigator of this project is the ability of stress to impair sustained attention, the process of monitoring situations for rare and unpredictably occurring events. Adequately sustaining attention is critical for accurately performing more complex cognitive tasks. Therefore, disruptions in sustained attention as a result of stress can lead to widespread cognitive impairments. Surprisingly, the neurobiological mechanisms that underlie the effect of stress on this type of attention are unknown. This project addresses this gap in knowledge by using behavioral, neuroanatomical, and molecular approaches to test how a specific stress-related chemical signal, corticotropin releasing factor, regulates the brain circuitry required for sustained attention in male and female rats. The results from this research will greatly advance our understanding of the interactions between the brain systems involved in stress and attention. These findings thereby may lay the groundwork for the development of strategies aimed at improving cognition during stressful events. In addition to the scientific work, this project includes an education plan designed to improve student learning outcomes for Temple University's diverse undergraduate population and create public resources for improving the teaching of college courses in the "flipped-classroom" format, in which students first learn new material outside of class and then use class time to work on exercises with classmates and the instructor.
Studies have examined how stress modulates learning, the neurobiological mechanisms by which stress modulates attention remain underexplored. Recently, the principal investigator of this project demonstrated that sustained attention is disrupted by central infusions of the stress-related neuropeptide, corticotropin releasing factor (CRF) in male and female rats. Sustained attention is known to be mediated by the basal forebrain. Therefore, this project examines how CRF regulates the basal forebrain from the systems to the molecular levels. Aim 1 is to test the hypothesis that CRF directly modulates the basal forebrain to disrupt sustained attention by combining pharmacological manipulations and a well-validated attention task. Aim 2 is to uncover the circuitry by which CRF can impact basal forebrain neurons by using retrograde tracing, cell-type specific markers, and measures of neuronal activation. Aim 3 is to identify molecular changes induced by CRF in cholinergic basal forebrain neurons by using Fluorescent Activated Cell Sorting in combination with next generation sequencing. The findings will improve our fundamental understanding of how stress affects cognition. The rich sequencing data resulting from this work is an important resource for researchers studying attention circuits, and is to be made publicly available for use by other investigators. The project's education plan is designed to improve the flipped-classroom format by developing special assignments that emphasize cognitive and metacognitive techniques to promote active engagement with the out-of-class material. These assignments are made available through public media and their efficacy is examined experimentally. The insights gained from the educational plan are to be published in education journals.
