Control of Noradrenaline in Learned Behaviors

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Noradrenaline is a critical neuromodulator that exerts widespread influence over most brain regions. However, despite its brain-wide effects, the conditions under which noradrenaline is released and how it affects different facets of behavior are still poorly understood. Neurons in the locus coeruleus, which are the predominant source of forebrain noradrenaline release, have been traditionally studied in the context of reflexive responses, such as the fight or flight behavior, but an explicit theory for its function in cognitive processes is lacking. The long-term objective of my research program is to understand the function of noradrenaline in learned behaviors. My background in Physics Engineering and Neuroscience situates my lab to pioneer and optimize methods to study noradrenergic circuits during sophisticated behaviors. In this proposal, we will focus on two distinct functions for the locus coeruleus in behavior: 1) noradrenaline enables behavioral execution and 2) facilitates learning of new task strategies. I previously shown that the temporal dynamics of locus coeruleus neuronal activity specifically supports these differential roles in an auditory detection task. During this task, I showed that transient noradrenergic activity occurs at the time of motor response and following a reinforcement, and silencing this activity impairs task execution and learning. I am now interested in understanding the distal and local circuits controlling this transient noradrenergic activity. We will focus our efforts on two main objectives: 1.Evaluate how locus coeruleus inhibitory neurons regulate noradrenergic activity during an auditory detection task. 2.Determine the contribution of top-down cortical inputs to noradrenergic responses during an auditory detection task. To achieve my research goals, I will expand the approach I have developed during my previous training. My lab will use a multidisciplinary research strategy, including targeted electrophysiological recordings, two-photon functional imaging, optogenetic and chemogenetic manipulations of neuronal activity, as well as computational analyses, to define neuronal encoding of learning and attention. Highly qualified personnel in my lab will use these in vivo techniques in transgenic mouse models to allow efficient targeting, manipulating, and recording of different neuronal populations. With this advanced neuroscience approach, my research program aims at generating a detailed theoretical framework for the yet unresolved role of LC-NA in learned behavior. Finally, the people joining my lab through this program will develop a range of skills from surgical methods, and behavioral design to circuit building, electrophysiology and optics. Learning these complementary skills will enable highly qualified personnel to become the next generation of multidisciplinary scientists.