Noradrenergic signaling in the rodent orbitofrontal cortex is required to update goal-directed actions.

Abstract

In a constantly changing environment, organisms must track the current relationship between actions and their specific consequences and use this information to guide decision-making. Such goal-directed behavior relies on circuits involving cortical and subcortical structures. Notably, a functional heterogeneity exists within the medial prefrontal, insular, and orbitofrontal cortices (OFC) in rodents. The role of the latter in goal-directed behavior has been debated, but recent data indicate that the ventral and lateral subregions of the OFC are needed to integrate changes in the relationships between actions and their outcomes. Neuromodulatory agents are also crucial components of prefrontal functions and behavioral flexibility might depend upon the noradrenergic modulation of prefrontal cortex. Therefore, we assessed whether noradrenergic innervation of the OFC plays a role in updating action-outcome relationships. We used an identity-based reversal task and found that depletion or chemogenetic silencing of noradrenergic inputs within the OFC rendered rats unable to associate new outcomes with previously acquired actions. Silencing of noradrenergic inputs in the medial prefrontal cortex or depletion of dopaminergic inputs in the OFC did not reproduce this deficit. Together, our results indicate that noradrenergic projections to the OFC are required to update goal-directed actions. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/498245v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@afc586org.highwire.dtl.DTLVardef@1d10ff4org.highwire.dtl.DTLVardef@6e6863org.highwire.dtl.DTLVardef@874b30_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIRats learn initial action-outcome associations in an instrumental task C_LIO_LINoradrenergic depletion in the OFC prevents the encoding and expression of these associations following reversal learning C_LIO_LIDopaminergic depletion in the OFC does not result in behavioral deficits C_LIO_LILC:OFC noradrenergic projections are required to update action-outcome associations C_LI IN BRIEFCerpa et al. investigate whether noradrenergic projections from the locus coeruleus (LC) to the orbitofrontal cortex are involved in updating previously established goal-directed actions following environmental change. They find that these LC projections are required to both encode and express reversed action-outcome associations in rats.