Abstract
Introduction: Adaptation requires sustained motivational control and task engagement to keep exploring and learning from action outcomes. In addition, to adapt performance, one must switch between decision and strategies. Engagement and switching are thus the key of flexibility. These functions involve multiple brain networks but the midcingulate cortex (MCC) and the locus coeruleus / noradrenergic (LC/NA) system play a central role. The MCC encodes outcome value during flexible behaviour, integrates outcome history and links it to action value. We recently demonstrated its causal role in task engagement by showing that stimulating its projections to dlPFC enhances task engagement. On the other hand, systemic studies have shown LC/NA involvement in task engagement, choice variability and the exploration-exploitation trade-off modulating frontal cortex signal efficiency and supporting cognitive flexibility. Yet, most studies are mainly systemic and could not provide insight on the specific role of LC/NA to frontal cortex.Since these regions project to one another, we investigated how the LC/NA to MCC projections contribute to flexible behaviour in Non-Human Primates?We hypothesized that enhancing NA input to MCC modifies neural dynamics and increases task engagement.To test this, we targeted LC/NA projections to the MCC in macaque using pathway-specific DREADDs. A retrograde Canine Adenovirus 2 vector expressing hM3Dq under the PRS promoter was injected into the MCC to limit expression to noradrenergic neurons. DREADDs were activated with 0.1mg/kg Deschloroclozapine (i.m) 20-30 minutes before behavioural testing. Behaviour was assessed in a three-arm bandit task (n=1), combined with chronic MCC LFP recordings. We analysed choices, exploratory shifts, response times and examined how NA modulation affect MCC LFPs.