Sofiya Hupalo of the Berridge Lab Wins Award

The Psychology Department is pleased to announce that Sofiya Hupalo, in Craig Berridge’s lab, has won the 2016 Ann E. Kelley Fellowship in Behavioral Neuroscience Travel award. 

Her abstract is below and she will present her poster at the Society for Neuroscience meeting in San Diego in November. 

Cognitive actions of corticotropin-releasing factor (CRF) across distinct prefrontal cortex (PFC)-dependent cognitive processes  - Sofiya Hupalo and Craig W. Berridge

The prefrontal cortex (PFC) regulates cognitive processes critical for flexible, goal-directed behavior. Dysfunction of PFC-dependent cognition is associated with a variety of psychopathologies, including ADHD. Although it has long been known that corticotropinreleasing factor (CRF) and CRF receptors are present in the PFC, the cognitive actions of CRF signaling in the PFC remain largely unknown. To test the hypothesis that CRF modulates PFC-dependent cognition, we first examined the

effects of intracerebroventricular (ICV; 0.1, 0.2, 1 μg) CRF on performance of rats in two tasks highly dependent on the PFC: 1) a spatial delayed-response test of working memory (t-maze) and 2) an operant-based signal detection test of sustained attention. In both tasks, ICV infusions of CRF elicited robust and dose-dependent impairments in performance. We then examined whether CRF acts within the PFC to modulate these PFC-dependent cognitive processes. As seen with ICV administration, intra-PFC infusions of CRF (25, 50, 100, 250 ng/hemisphere) impaired working memory performance. This action was topographically organized, such that working memory impairment was only observed with CRF infusion into the caudal aspect of the dorsomedial PFC (dmPFC). However, in contrast to that seen with working memory, CRF infusions (25, 50, 250 ng/hemisphere) into either the caudal or rostral dmPFC had no effect on sustained attention.

Subsequent studies investigated the degree to which endogenous CRF signaling modulates PFC-dependent cognition using the CRF antagonist, D-Phe-CRF. Both ICV (2, 4, 10 μg) and intra-dmPFC (50, 200 ng/hemisphere) infusions of this antagonist dose-dependently improved working memory performance. ICV infusion of this antagonist similarly elicited dose-dependent improvement in sustained attention. Collectively, these observations indicate that CRF modulation of multiple PFC-dependent

cognitive processes involves differing neurocircuitry, with working memory involving CRF receptor signaling within the PFC. This research provides novel insight into the neurobiology of PFC-dependent cognition and may have relevance for treating psychopathologies associated with PFC dysfunction. For example, FDA approved treatments for ADHD improve performance in tasks of working memory and sustained attention in rodents and humans. Given a CRF antagonist also improves PFC-dependent cognition, this may represent a novel pharmacological approach for the treatment of ADHD and other disorders associated with PFC-dependent cognitive dysfunction.


 

This fellowship, honoring the legacy of Ann E. Kelley, supports the training of future generations of behavioral neuroscientists that embody Ann Kelley's passion for understanding the brain with the ultimate goal of using this knowledge to reduce human suffering

Dr. Kelley led an eminent career in which she made groundbreaking contributions to neuropsychopharmacology. She held faculty positions at the University of Bordeaux in France, Harvard University, Northeastern University, and the University of Wisconsin, where she was the Wisconsin Distinguished Neuroscience Professor, Professor of Psychiatry, and Director of the Neuroscience Training Program. She published over 130 peer-reviewed scientific papers and her work was funded continuously for over two decades by the National Institutes of Health and the National Science Foundation. She was recognized with a MERIT award from the National Institute on Drug Abuse, an invited lecture at a Nobel Symposium in Stockholm, and the Mika Salpeter Lifetime Achievement Award from the Society for Neuroscience. Dr. Kelley was a pioneer in science and launched the successful careers of a generation of neuroscientists through her mentoring and teaching.