RT Journal Article SR Electronic T1 Activation of subthalamic nucleus stop circuit disrupts cognitive performance JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0159-20.2020 DO 10.1523/ENEURO.0159-20.2020 A1 Jonathan Heston A1 Alexander Friedman A1 Mustafa Baqai A1 Nicholas Bavafa A1 Adam R. Aron A1 Thomas S. Hnasko YR 2020 UL http://www.eneuro.org/content/early/2020/09/03/ENEURO.0159-20.2020.abstract AB Much evidence supports a fundamental role for the subthalamic nucleus (STN) in rapidly stopping behavior when a stop signal or surprising event occurs, but the extent to which the STN may be involved in stopping cognitive processes is less clear. Here we used an optogenetic approach to control STN activity in a delayed-match-to-position (DMTP) task where mice had to recall a response location after a delay. We first demonstrated that a surprising event impaired performance by both slowing the latency to respond and increasing the rate of errors. We next showed that these effects could be mimicked by brief optogenetic activation of the STN. Further, inhibiting STN during surprise blocked surprise-induced slowing, though without changing surprise-induced errors. These data are consistent with the hypothesis that STN is recruited by surprise to slow responding and that this can also interrupt cognitive processes. Under normal conditions STN-mediated stopping of behavior may slow or stop ongoing cognition to facilitate cognitive reorienting and adaptive responses to unexpected sensory information, but when malfunctioning it could produce pathologies related to over-rigidity or increased distractibility.SIGNIFICANCE STATEMENT While a central role for STN in slowing and stopping behavior is well established, recent studies in human subjects have expanded this idea and suggest that STN-related circuits that stop behavior can also stop cognitive processes, i.e., thought. To test this, we developed a cognitive task in mice. We show that surprising sensory stimuli and optogenetic STN activation similarly slow responding and increase error rate. Inhibition of the STN during surprise also increased error rate, but blocked the surprise-effect on response speed. These results support a more general role for the STN in stopping not only action but also cognition.