Grant: Discovery Grants Program - Individual

Nature of the research: A most fundamental question in neuroscience is concerned with how the brain learns. According to formal computational analyses, learning occurs expectations fail to match reality, that is, when there is a prediction error. The greater the error, the greater the learning. The Ventral Tegmental Area (VTA) dopamine (DA) signal tracks reward prediction errors. The focus on reward learning ignores that biological organisms also learn about aversive events. Here, we will extend our understanding of the VTA DA signal in the aversive domain. We already have evidence linking VTA DA transients to aversive prediction error. Using interrogation methods we will examine whether VTA DA transients influence not only whether learning takes place (i.e., conditions for learning) but also the nature of the learning that occurs (i.e., content of learning). Specifically, using optogenetic modulation of VTA DA transients to determine if they regulate i) excitatory (learning about the presence of events) and ii) inhibitory (learning about the absence of events) associations in fear learning in line with formal learning theory. To gain a holistic understanding of the role of the VTA DA signal in associative learning, we will monitor neural dynamics under conditions when appetitive and aversive information interact as well as use interrogation methods to uncover a potential causal role. Importance and benefit. Understanding how the brain is able to predict upcoming appetitive and aversive events is critical to adaptive functioning. Furthermore, the VTA DA signal is in a position to broadcast prediction error information across the brain to influence learning, and knowing how this information is processed for events of dissociable valence will help understand how associations are formed in brain areas downstream. Lastly, having gained a basic knowledge of these neural processes, the field can use this information to inform machine learning algorithms that use appetitive and aversive outcomes to control behaviour as well as embark on research aimed at delineating how prediction error processes break down in reward- and fear-related disease states. Therefore, the proposed research will be of value not only researchers within the basic neuroscience field working on learning and memory, but will also inform the work of computational modelers, engineers, artificial intelligence and clinical neuroscientists, providing a broad benefit to Canadian society and beyond. Outcomes. The research proposed will build the basic science platform aimed at understanding associative learning in the appetitive and aversive domains. Through publications, conference presentations, outreach and podcasts we will reach not only scientists but also the wider public. Beyond research acquisition, our goal is to train new researchers to gain new practical skills and conceptual knowledge, preparing them for future careers in academia, industry, government or the clinic.