The role of noradrenaline in signaling prediction error and promoting learning

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Predictive learning is highly adaptive; it allows us and other animals to use information in the environment to anticipate and prepare for biologically significant events. Equally important is the ability to update previous learning when environmental conditions change, and the organism's predictions about impending events are no longer accurate. This project examines the role of the neurotransmitter noradrenaline (NA) in this particular form of error-driven learning. Detecting and encoding relationships between events and, in particular, modifying previous learning when confronted with new information is essential for adaptive, flexible control of behaviour. However, we still know very little about the neural systems that make this possible. While substantial research implicates dopamine (DA) in initial learning about rewarding events, recent research conducted by Dr. Corbit has shown that updating this learning, notably in extinction (when expected reinforcement is omitted), involves noradrenaline (NA). Critical questions remain regarding the broader role of NA in in signaling reward prediction errors and how this activity translates into new learning. This research program will adopt a multidisciplinary approach. We will use a battery of sophisticated behavioural tasks specifically designed to manipulate prediction error. These behavioural methods will be combined with state of the art neuroscience methods that record (in vivo electrophysiology) and manipulate (optogenetics; pharmacological treatments) neural activity during ongoing behavioural tasks with temporal and spatial precision unsurpassed by other methods to define the role of NA in signaling prediction error and driving learning. This work will be of wide interest because it addresses basic questions about motivation, arousal and reinforcement learning. This project is significant because establishing and updating knowledge about the relationship between events in the world is a fundamental capacity essential for adaptive behaviour and failure to flexibly modify previously learned responses is central to a number of neuropsychiatric diseases including dementia, depression, drug addiction and attention deficit hyperactivity disorder (ADHD). To understand pathology of this kind requires insight into the neural bases of learning and attention in the healthy brain. If NA plays a major role in either error-driven learning in general or specifically in the updating of learning when conditions change, then this has major implications for our conception of the neurobiology of learning. In addition, this research program provides a multidisciplinary training environment, with specified roles for postdoctoral fellows, graduate students and undergraduate students and numerous opportunities for trainees to develop a wide range of research skills from the conception of the question and hypothesis, design of experiments, to data collection and interpretation, and finally manuscript preparation.