Unilateral Optogenetic Inhibition and Excitation of Basal Ganglia Output Affect Directional Lick Choices and Movement Initiation in Mice.

Models of basal ganglia (BG) function predict that tonic inhibitory output to motor thalamus (MT) suppresses unwanted movements, and that a decrease in such activity leads to action selection. Further, for unilateral activity changes in the BG, a lateralized effect on contralateral movements can be expected due to ipsilateral thalamocortical connectivity. However, a direct test of these outcomes of thalamic inhibition has not been performed. To conduct such a direct test, we utilized rapid optogenetic activation and inactivation of the GABAergic output of the substantia nigra pars reticulata (SNr) to MT in male and female mice that were trained in a sensory cued left/right licking task. Directional licking tasks have previously been shown to depend on a thalamocortical feedback loop between ventromedial MT and antero-lateral premotor cortex. In confirmation of model predictions, we found that unilateral optogenetic inhibition of GABAergic output from the SNr, during ipsilaterally cued trials, biased decision making towards a contralateral lick without affecting motor performance. In contrast, optogenetic excitation of SNr terminals in MT resulted in an opposite bias towards the ipsilateral direction confirming a bidirectional effect of tonic nigral output on directional decision making. However, direct optogenetic excitation of neurons in the SNr resulted in bilateral movement suppression, which is in agreement with previous results that show such suppression for nigral terminals in the superior colliculus (SC), which receives a bilateral projection from SNr.