The neurobiology of learning from rewards and mistakes

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The overall goal of my research is to understand how the brain makes choices. Humans and animals have a tremendous capacity to adapt choices based on experience, but neural choice mechanisms can sometimes produce irrational outcomes, particularly under heightened affective states such as arousal or stress. The long-term vision of my research program is to develop a comprehensive theory of neurobiological choice mechanisms that can account for both experience-based adaptation of choice and its modulation by affective states. Many current theories posit that the brain has at least two distinct systems that can control choice: a `goal' system that uses reward outcomes to adapt choices quickly; and a `habit' system that adapts choices slowly. My recent NSERC-funded work led to an unexpected breakthrough discovery that the habit system can drive rapid adaptation of choice following choice errors, which contradicts most prevailing theories and indicates that major revisions are needed. The short-term objectives of my research program over the next 5 years are to capitalize on this discovery and other recent findings to discover how the neuromodulator dopamine influences choice adaptation by influencing the dynamical interaction between goal and habit systems. Specifically, my short-term objectives are to discover how brief bursts and pauses of dopamine neurons affect (1) behavioural choice after errors, (2) functional signaling between neural structures involved in habit and goal systems, and (3) the stability and error information in ensemble spiking neural activity in the habit system. This is essential new information needed for understanding the neural mechanisms of trial-and-error choice adaptation, and for discovering how choices are influenced by dopamine-related affective states, such as stress and arousal. This research is also a key step for my future objectives of elucidating reciprocal interactions between choice adaptation, neural signaling, genetic/epigenetic regulation, and dysregulated affective states. I will leverage my state-of-the-art laboratory for integrated in vivo electrophysiological, pharmacological, and optogenetic techniques in rodents to undertake an extensive quantitative investigation of the mechanisms by which dopamine modulation rapidly affects ongoing neural dynamics to influence choice. My multidisciplinary research program and cell-to-systems research approach provides exceptional training for HQP, and is poised for transformative advances in our theory of decision-making at both molecular and systems levels, which has potential impact on a range of societal and economic needs stemming from impaired learning and poor choices. Moreover, the advanced analytical tools developed in this research will accelerate emerging technology, such as my ongoing commercialization of functional brain state detection in humans.