Monoaminergic neuromodulation of cortical circuits underlying economic investment decisions

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We attempt to make decisions that best serve our goals. Yet in complex environments, both the source and timing of future outcomes is uncertain. Humans and other animals must therefore adjust their investments of limited resources – whether time, effort, or money – according to the risk in obtaining positive outcomes. Orbitofrontal cortex (OFC) contributes to these economic investment decisions by computing the value of uncertain outcomes. However, the mechanisms by which OFC dynamically computes value remain largely unknown. Neurons releasing monoaminergic neuromodulators such as dopamine and serotonin broadcast value signals to many brain regions including OFC and could therefore enable economic investment decisions. However, it remains elusive (i) how dopamine and serotonin control OFC neurons and networks thereby adjusting economic investment decisions and (ii) if and how OFC circuits, in turn, inform neuromodulatory centers about the value of uncertain outcomes. The goal of my proposal is to determine the mechanisms by which monoaminergic neuromodulators interact with cortical networks to enable economic investment decisions. Specifically, my research will address: (1) what is the network architecture in OFC that supports economic investment decisions? (2) How do monoaminergic neuromodulators such as dopamine and serotonin control OFC networks to adjust economic investment decisions? (3) What are the cortico-neuromodulatory feedback mechanisms that inform neuromodulatory signals? I will address these questions by combining a model-based behavioral approach in rats with state-of-the-art optogenetic, electrophysiological and computational tools. This will allow us to record a large number of neurons and simultaneously measure and control cortical release of monoaminergic neuromodulators such as dopamine and serotonin to determine their causal impact on cortical networks. In addition, a combination of retrograde viral strategies and optogenetic tools will allow to selectively measure and manipulate cortical projection neurons to neuromodulatory centers thereby determining their causal role for investment decisions. These experiments will yield novel mechanistic insight into the cortical circuit architecture for economic decisions. My proposal will reveal principles of neuromodulatory control of cortical neurons and networks that will delineate the functional roles of monoaminergic neuromodulation for decision-making.