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Noradrenergic modulation of the orbitofrontal cortex mediates flexibility of goal-directed behavior

Cerpa J-C, Marchand AR, Wolff M, Parkes SL, Coutureau E (2018) Noradrenergic modulation of the orbitofrontal cortex mediates flexibility of goal-directed behavior. Neuroscience 2018 Abstracts 325.09 / DDD22. Society for Neuroscience, San Diego, CA.

Summary: For an organism, knowledge of the consequences of its actions and the ability to assign a value to these consequences are both crucial processes allowing an appropriate goal-directed response. The major role of prefrontal regions, e.g. insular and medial prefrontal cortices, for these processes has been very well described. However, the mechanism by which the organism quickly adapt this goal-directed response to unexpected environmental changes remains unknown. It is possible to study this ability using instrumental learning. Typically, during an initial phase, an animal must associate voluntary actions with the delivery of rewarding outcomes. Then, during a reversal phase, the animal must respond flexibly to a modification of these associations. Using this task and chemogenetic tools allowing specific inhibition of cerebral regions, we have recently demonstrated a crucial role of the ventrolateral orbitofrontal cortex (vlOFC) for flexible response adaptation during the reversal phase (Parkes et al., 2017). In the present study, we focused on the noradrenaline (NA) input to the vlOFC which has been commonly implicated in flexibility-requiring tasks. In a first experiment, using a toxin (anti-DβH saporin) we selectively depleted noradrenergic fibers in the vlOFC and showed a deficit of behavioral flexibility. Notably, this effect was not only specific to the reversal phase but also to vlOFC input since a similar depletion restricted to the medial portion of the prefrontal cortex had no effect. Using an intersectional chemogenetic approach aiming at selectively targeting the locus cœruleus (LC) input to the vlOFC, we are deciphering the time course of the involvement of this pathway during behavioural flexibility. Taken together, these results demonstrate a central role for noradrenaline input to the vlOFC in behavioural flexibility and reinforce the idea that the LC exerts a strong modulation of OFC functions.

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