CONTEXT-DEPENDENT ROLES OF DORSAL STRIATUM MEDIUM SPINY NEURON POPULATIONS IN FLEXIBLE BEHAVIOUR

Flexible behaviour requires animals to select different actions in response to the same sensory stimuli in distinct cognitive contexts. The dorsal striatum may play a central role in this process given its role in facilitating action selection and suppression via D1- and D2- receptor expressing medium spiny neurons (MSNs). Directly manipulating D1- or D2-MSN activity influences movements in broadly predictable ways. However, it is unclear whether MSN outputs are shaped by different cognitive contexts. Here, we investigated the role of MSNs in context-dependent action selection and suppression in two striatal subregions, the dorsomedial striatum (DMS) and ventrolateral striatum (VLS). We studied mice as they performed a block-wise task-switching behaviour where the same visual stimuli were either relevant or irrelevant to the task. As expected, optogenetically inhibiting D2-MSNs in the VLS resulted in a failure to suppress lick responses to an unrewarded visual stimulus. However, this effect was greater when the visual stimuli were behaviourally relevant, despite identical optogenetic and visual stimuli. Similarly, activating D1-MSNs in the VLS evoked significantly more incorrect licking to the same visual stimulus when it was behaviourally relevant. Similar effects were observed in the DMS. We measured D2-MSN population activity in the VLS using fibre photometry and found responses aligned to stimuli and licking. However, after correcting for subthreshold mouth movements, these responses did not differ across task contexts. These results reveal the strong influence of abstract cognitive context on sensorimotor transformations in the basal ganglia.