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The Levinson Emerging Scholars Program

Nile Graddis - Psychology

Nile GraddisNile Graddis is currently a senior majoring in Psychology. He became involved in research as a sophomore working in Dr. Mizumori's lab. Nile is interested in examining the neurobiology of learning and memory because of the critical contributions that learning makes to human as well as animal behavior. He hopes that by elucidating some of the basic mechanisms of learning, we might be better able to help those with learning disabilities or addictions. In Dr. Mizumori's lab Nile has used electrophysiological and behavioral methods to explore the role of burst dopamine release on hippocampal place cell activity and local field potentials. His current research focuses on the influence of striatal projection neurons to modulation of learning rate. He seeks to use pharmacological, behavioral, and electrophysiological techniques to better understand the contributions that the neurons of distinct striatal projection pathways make to the activity of midbrain dopamine neurons and to learning. In his spare time, Nile enjoys reading and spending time with his friends.

Mentor: Sheri Mizumori, Psychology

Project Title: Understanding the roles of striatal projection neurons in modulating prediction error signaling

Abstract: How do we learn from our mistakes? One interesting possibility is that dopamine neurons in the midbrain compute a prediction error signal, which reflects the difference between expected and received rewards. This signal, which has been observed at the level of individual neurons, can then inform learning and future behavior. Despite the potential importance of this signal, the brain systems that modulate it are not well understood. Neurons of the ventral striatum project reciprocally to midbrain dopamine neurons, and may thus be involved in modulating the prediction error signal. These neurons project along two pathways, the direct striatonigral pathway and the indirect striatopallidal pathway, which have historically been difficult to manipulate separately. Recent advances in optogenetics and pharmacogenetics have made study of the pathways possible, leading to findings that these two populations of neurons antagonistically modulate learning. I propose to extend these behavioral findings by using electrophysiological and pharmacogenetic techniques in concert to investigate the roles that these distinct pathways play in modulating prediction error signaling. I will assess reward prediction signaling in midbrain dopamine neurons as rats learn on a two-choice operant maze task. I will use designer receptors exclusively activated by designer drugs to selectively inactivate neurons of the two striatal populations as rats perform this task. This will allow me to assess the roles played by neurons of these populations in modulating prediction error signaling. I hypothesize that inactivating one population of striatial neurons (striatonigral) will inhibit learning and impede the development of prediction error signaling while inactivating the other (striatopallidal) will have opposite effects. This work will provide valuable insight into the neural processes through which we learn from our mistakes. Such knowledge may allow us to provide better help to people suffering from addictive or compulsive behavioral disorders.