ESTABLISHING NEUROMODULATORY MECHANISMS UNDERLYING COST-BENEFIT MODULATION OF VIGOUR THROUGH AN EFFORT-BASED FORAGING TASK

Animals modulate the timing and speed of their movements to reach rewards sooner rather than later (i.e., they trade effort to save time). The basal ganglia and in particular the dorsal striatum (DS), is known to refine the timing and speed of reward-oriented movements. While it has been shown that substantia nigra derived dopamine is critical for adaptive vigour, how serotonin from the dorsal raphe nucleus (DRN) may modulate this is unknown. We developed an effort-based foraging task in which mice run back and forth in a corridor to obtain rewards. A key aspect of the task is that the running distance can be manipulated to increase the effort required. We found that mice reliably increased their running speed as distance increased, in order to maintain a high reward rate. Then, we investigated a putative circuit for the integration of effort and reward to modulate movement vigour between the locus coeruleus (LC), DRN and DS. Using optogenetics and fiber photometry, we showed that the noradrenergic projection from the LC activates dopaminergic neurons within the DRN that locally modulate serotonergic neurons projecting to the DS (Nava et al., in preparation). Using a DREADDs approach to inhibit LC terminals in the DRN during foraging, we found that mice exhibit a reduction in movement vigour under conditions of higher effort cost. Future work will investigate whether and how serotonin might contribute to adaptive effort-time tradeoff. This work has implications for the field of bioenergetics and movement disorders like Parkinson’s Disease.