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Uncertain decisions shape daily life, from choosing a meal off a menu to taking a leap toward an uncertain future, yet the neural mechanisms guiding these choices remain poorly understood. My research has explored the neural basis of uncertainty in decision-making, particularly in cost-benefit and approach-avoidance contexts, using mouse models relevant to neurodegeneration and neuropsychiatric disorders. Currently in the Graybiel laboratory at MIT's McGovern Institute, I study approach-avoidance decision-making using paradigms derived from human clinical models and non-human primate approach-avoidance assays that assess individual risk evaluation and mood-related phenotypes. This builds on my previous work evaluating approach-avoidance behavior and striosomal function in Huntington's disease model mice, a striatal disease accompanied by a high prevalence of mood dysfunction in which affected patients exhibit striosomal vulnerability. We recently discovered that the nociceptin system, a pain-related peptide known to antagonize dopamine, is highly expressed in striosomal neurons that directly project to the dopamine system, positioning it as a potential therapeutic target for depression as well as Parkinson's disease. My research foundation was established during training in the laboratories of Professors Susumu Tonegawa (MIT) and Naoshige Uchida (Harvard), where I demonstrated how dopamine-based reinforcement biases perceptual decisions under conditions of low confidence and collaborated on evaluating how serotonergic neurons bias cost-benefit decision-making in the form of delay discounting.
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