Investigating the roles of dorsomedial striatal projection neurons in goal-directed action

A critical element of animal behaviour is learning the relationship between actions and their consequences, and maintaining flexibility in such actions when environmental conditions change is essential for sustaining goal-seeking behaviour. It is well accepted that the posterior region of dorsomedial striatum (pDMS) is necessary for learning and performing goal-directed actions, however, the specific roles of pDMS spiny projection neurons (SPN), which project either directly (dSPNs) or indirectly (iSPNs) to basal ganglia output structures remains largely unknown. Here, we examined the relative contributions of pDMS dSPNs and iSPNs in various aspects of goal-directed action learning and performance, utilizing modern neuronal tract tracing, electrophysiology, chemogenetics and optogenetics. We found that instrumental lever-press training produced an increase in cellular activity in dSPNs that was specific to the response being learned; the increase was observed in the hemisphere contralateral to the lever. We demonstrated that suppressing activity in dSPNs during training abolished goal-directed learning, as rats did not display goal-directed action in a drug-free choice test following outcome devaluation, despite pathway restoration. We saw no disruption following iSPN suppression, or stimulation, suggesting that goal-directed learning relies on dSPNs specifically and is not attributable to the relative balance of dorsal striatal output between the direct and indirect pathways. During instrumental performance, we found that unilaterally suppressing dSPNs but not iSPNs biased choice to the instrumental response ipsilateral to the hemisphere of suppression however we saw no effect of bilaterally suppressing either population on goal-directed performance in relation to changes in outcome value. This suggests that dSPNs are important for driving the performance of the learned instrumental response, and that the relative value of each response is maintained following a bilateral reduction in the activity of either output pathway. We found that iSPNs were important for response flexibility more generally; suppression of activity in iSPNs but not dSPNs reduced rats’ efficiency in a task requiring flexible response reversal. Together, therefore, dSPNs and iSPNs play distinct and specific roles in goal-directed action learning and performance by way of integrating learning signals provided by striatal inputs and translating these into performance through basal ganglia output structures