Striatal indirect pathway mediates exploration via collicular competition

• Published in: Nature (London) 2021-11, Vol.599 (7886), p.645-649
• Main Authors: Lee, Jaeeon, Sabatini, Bernardo L.
• Format: Article
• Language: English
• Subjects: 631/1647/2253; 631/378/2632/1323; 631/378/3920; 64/110; Animals; Basal ganglia; Basal Ganglia - cytology; Basal Ganglia - physiology; Behavior; Behavior, Animal - physiology; Brain research; Circuits; Competition; Corpus striatum; Corpus Striatum - cytology; Corpus Striatum - physiology; Deactivation; Decision Making; Exploration; Exploratory Behavior - physiology; Female; Ganglia; Hemispheres; Humanities and Social Sciences; Hypotheses; Inactivation; Male; Mice; multidisciplinary; Neostriatum; Neural circuitry; Neural Inhibition - physiology; Neural Pathways - physiology; Neurons - physiology; Optogenetics; Physiological aspects; Reward; Science; Science (multidisciplinary); Superior colliculi; Superior Colliculi - cytology; Superior Colliculi - physiology; Superior colliculus
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-04055-4

The ability to suppress actions that lead to a negative outcome and explore alternative actions is necessary for optimal decision making. Although the basal ganglia have been implicated in these processes 1 – 5 , the circuit mechanisms underlying action selection and exploration remain unclear. Here, using a simple lateralized licking task, we show that indirect striatal projection neurons (iSPN) in the basal ganglia contribute to these processes through modulation of the superior colliculus (SC). Optogenetic activation of iSPNs suppresses contraversive licking and promotes ipsiversive licking. Activity in lateral superior colliculus (lSC), a region downstream of the basal ganglia, is necessary for task performance and predicts lick direction. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly excites contralateral lSC, explaining the emergence of ipsiversive licking. Optogenetic inactivation reveals inter-collicular competition whereby each hemisphere of the superior colliculus inhibits the other, thus allowing the indirect pathway to disinhibit the contralateral lSC and trigger licking. Finally, inactivating iSPNs impairs suppression of devalued but previously rewarded licking and reduces exploratory licking. Our results reveal that iSPNs engage the competitive interaction between lSC hemispheres to trigger a motor action and suggest a general circuit mechanism for exploration during action selection. Indirect striatal projection neurons in the basal ganglia modulate activity in the superior colliculus, thereby controlling selection and exploration of actions in response to a  reward omission.