Role of the orbitofrontal cortex in learning of goal-directed action

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Humans and animals select and perform previously learned actions in adaptive ways to obtain specific goals such as food, a capacity that is essential to survive in an ever-changing environment. A fundamental challenge of neuroscience is to understand the neural basis of decision making processes underlying selection and performance of goal-directed action. For instance, to make adaptive decisions, it is not only vital to retrieve information about learned relationships between actions and their consequences. It is also necessary to evaluate whether the expected value or benefits of an action make it worth tolerating the efforts or costs to obtain it and to analyze current situational factors such as motivational states (e.g. hunger). Thus, actual costs and benefits of the available response options must be weighed before deciding which course of action to choose. Our recent data suggest that the medial orbitofrontal cortex (mOFC) is a key component of a neural network that critically supports such processes. However, the specific involvement of the mOFC as well as its interactions with other key components of the underlying neural network is, as yet, largely unknown. In this project, we will combine pharmacological, optogenetic and neural circuit analysis methods to examine the role of the mOFC and pathways linking the mOFC with the nucleus accumbens in rats performing complex cognitive tasks that allow for a detailed analysis of behavioral processes underlying action selection. This research will be complemented by an assessment of molecular markers of neuronal activity in involved brain areas. Our goal is to provide a detailed description of how the mOFC contributes to selection and performance of goal-directed action and highlight functional interactions with the nucleus accumbens, a known key component of the underlying neural network, on a molecular, neural and behavioral level. This research possibly allows important new insights into the exact role of the mOFC in decision making which is still elusive. Our findings could also pave the way for a deeper understanding of impaired decision making and action selection in neuropsychiatric disorders with prefrontal dysfunction such as major depression.