@article {Hormigo1529, author = {Sebastian Hormigo and Ji Zhou and Dorian Chabbert and Bharanidharan Shanmugasundaram and Manuel A. Castro-Alamancos}, title = {Basal Ganglia Output Has a Permissive Non-Driving Role in a Signaled Locomotor Action Mediated by the Midbrain}, volume = {41}, number = {7}, pages = {1529--1552}, year = {2021}, doi = {10.1523/JNEUROSCI.1067-20.2020}, publisher = {Society for Neuroscience}, abstract = {The basal ganglia are important for movement and reinforcement learning. Using mice of either sex, we found that the main basal ganglia GABAergic output in the midbrain, the substantia nigra pars reticulata (SNr), shows movement-related neural activity during the expression of a negatively reinforced signaled locomotor action known as signaled active avoidance; this action involves mice moving away during a warning signal to avoid a threat. In particular, many SNr neurons deactivate during active avoidance responses. However, whether SNr deactivation has an essential role driving or regulating active avoidance responses is unknown. We found that optogenetic excitation of SNr or striatal GABAergic fibers that project to an area in the pedunculopontine tegmentum (PPT) within the midbrain locomotor region abolishes signaled active avoidance responses, while optogenetic inhibition of SNr cells (mimicking the SNr deactivation observed during an active avoidance behavior) serves as an effective conditioned stimulus signal to drive avoidance responses by disinhibiting PPT neurons. However, preclusion of SNr deactivation, or direct inhibition of SNr fibers in the PPT, does not impair the expression of signaled active avoidance, indicating that SNr output does not drive the expression of a signaled locomotor action mediated by the midbrain. Consistent with a permissive regulatory role, SNr output provides information about the state of the ongoing action to downstream structures that mediate the action.SIGNIFICANCE STATEMENT During signaled active avoidance behavior, subjects move away to avoid a threat when directed by an innocuous sensory stimulus. Excitation of GABAergic cells in the substantia nigra pars reticulata (SNr), the main output of the basal ganglia, blocks signaled active avoidance, while inhibition of SNr cells is an effective stimulus to drive active avoidance. Interestingly, many SNr cells inhibit their firing during active avoidance responses, suggesting that SNr inhibition could be driving avoidance responses by disinhibiting downstream areas. However, interfering with the modulation of SNr cells does not impair the behavior. Thus, SNr may regulate the active avoidance movement in downstream areas that mediate the behavior, but does not drive it.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/41/7/1529}, eprint = {https://www.jneurosci.org/content/41/7/1529.full.pdf}, journal = {Journal of Neuroscience} }