Striatal indirect pathway mediates action switching via modulation of collicular dynamics

Type 2 dopamine receptor-expressing, or indirect pathway striatal projection (iSPNs), neurons comprise one of two major pathways through the basal ganglia[1][1], and are a major drug target for treatment of neuropsychiatric disorders[2][2]–[4][3]. The function of iSPNs is unclear with proposed roles in suppression of unwanted actions and in refining selection actions or their kinematics[5][4]–[12][5]. Here, we show that iSPNs can simultaneously suppress and facilitate conflicting motor actions in a lateralized licking task. Activation of iSPNs suppresses contraversive while promoting ipsiversive licking, allowing mice to rapidly switch between alternative motor programs. iSPN activity is prokinetic even when mice are not cued to perform an action. Activity in lateral superior colliculus (lSC), a basal ganglia target, is necessary for performing the task and predicts action. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly, excites contralateral lSC. iSPN activity has neuron-specific effects that, at the population level, steers the neural trajectory towards that associated with ipsiversive licking. Thus, our results reveal a previously unknown specificity of iSPNs effects on downstream brain regions, including the ability to excite contralateral regions and trigger motor programs. These results suggest a general circuit mechanism for flexible action switching during competitive selection of lateralized actions. ### Competing Interest Statement Dr. Sabatini is a founder and holds private equity in Optogenix. Tapered fibers are commercially available from Optogenix were used as tools in the research. [1]: #ref-1 [2]: #ref-2 [3]: #ref-4 [4]: #ref-5 [5]: #ref-12