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The anatomy and functions of the rodent prefrontal cortex (PFC) have been extensively studied. It is now clear that the PFC is at the core of various executive functions and that these functions depend on monoaminergic neuromodulation. The PFC receives extensive projections from monoaminergic nuclei and, in particular, from the locus cœruleus (LC) which is the major source of noradrenaline (NA) in the cortex. Projections of this nucleus have long been considered to act diffusely and uniformly throughout the entire brain. However, recent studies have revealed a separate innervation of prefrontal sub-regions by non-collateralizing LC neurons, suggesting a specific modulation of their functions. Following this idea, we aimed at describing more precisely the pattern of noradrenergic innervation into different orbital (OFC) and medial (mPFC) sub-regions of the PFC. We focused on the lateral (LO), ventral (VO) and medial (MO) portions of the OFC, and on areas 32d (A32d), 32v (A32v) and 25 (A25) in the mPFC. Using Dopamine-β-Hydroxylase as a specific noradrenergic marker, we performed an automatic quantification of noradrenergic fibers and varicosities in each of these sub-regions. The results indicate that noradrenergic innervation is heterogeneous in some prefrontal sub-regions along the rostro-caudal axis. Functional dissociations have been recently reported in prefrontal sub-regions along the rostro-caudal direction. Our findings add neuroanatomical support to this emergent idea.

Techniques that allow the manipulation of specific neural circuits have greatly increased in the past few years. DREADDs (Designer receptors exclusively activated by designer drugs) provide an elegant way to manipulate individual brain structures and/or neural circuits, including neuromodulatory pathways. Considerable efforts have been made to increase cell-type specificity of DREADD expression while decreasing possible limitations due to multiple viral vectors injections. In line with this, a retrograde canine adenovirus type 2 (CAV-2) vector carrying a Cre-dependent DREADD cassette has been recently developed. In combination with Cre-driver transgenic animals, the vector allows one to target neuromodulatory pathways with cell-type specificity. In the present study, we specifically targeted catecholaminergic pathways by injecting the vector in knock-in rat line containing Cre recombinase cassette under the control of the tyrosine hydroxylase promoter. We assessed the efficacy of infection of the nigrostriatal pathway and the catecholaminergic pathways ascending to the orbitofrontal cortex (OFC) and found cell-type-specific DREADD expression.

International audience; The medial prefrontal cortex (mPFC) has long been considered a critical site in action control. However, recent evidence indicates that the contribution of cortical areas to goal-directed behavior likely extends beyond mPFC. Here, we examine the function of both insular (IC) and ventrolateral orbitofrontal (vlOFC) cortices in action-dependent learning. We used chemogenetics to study the consequences of IC or vlOFC inhibition on acquisition and performance of instrumental actions using the outcome devaluation task. Rats first learned to associate actions with desirable outcomes. Then, one of these outcomes was devalued and we assessed the rats' choice between the 2 actions. Typically, rats will bias their selection towards the action that delivers the still valued outcome. We show that chemogenetic-induced inhibition of IC during choice abolishes goal-directed control whereas inhibition during instrumental acquisition is without effect. IC is therefore necessary for action selection based on current outcome value. By contrast, vlOFC inhibition during acquisition or the choice test impaired goal-directed behavior but only following a shift in the instrumental contingencies. Our results provide clear evidence that vlOFC plays a critical role in action-dependent learning, which challenges the popular idea that this region of OFC is exclusively involved in stimulus-dependent behaviors.