Abstract
The functional role of basal ganglia receiving territory of the motor thalamus (BGMT) remains poorly understood. Therefore, to examine how basal ganglia output via the substantia nigra pars reticulata (SNr) and projections to the BGMT control motor behavior, we unilaterally inhibited or excited basal ganglia output neurons and their projections to the BGMT during periods of movement preparation and initiation in mice performing a 2-alternative choice licking task. Using a viral vector carrying the inhibitory opsin DIO-ARCH3 into the SNr of VGAT-cre mice, we inhibited SNr activity starting 0.5 s before the onset of a response window where the mouse must lick right or left depending on the location of a previously delivered air-puff stimulus to the right or left whiskers, respectively. Light activation of ARCH3 in the SNr inhibited SNr activity and biased lick responses towards the lick spout contralateral to the hemisphere of stimulation. In another set of mice, we excited SNr activity using a fast variant of the ChR2 opsin (DIO-hChR2-E123A/T159C), which suppressed licking activity irrespective of the direction of the trial. However, exciting terminals of neural projections from the SNr to the BGMT biased licking responses to the lick spout ipsilateral to the stimulation. These results demonstrate the role of the SNr in directing movement preparation and initiation in behaving mice, broadly supporting classic models of the basal ganglia where decreases in BG output activity act to facilitate voluntary movement through thalamo-cortical pathways.
Significance Statement This study provides the first evidence of fast reversible manipulations of basal ganglia output directly influencing motor responses. This is also the first study to begin to isolate the effects of basal ganglia output specifically to the motor thalamus on the control of motor behavior. We found that inhibiting the SNr directly led to a contralateral bias in the licking motor response and that direct activation of the SNr suppressed licking activity altogether. Interestingly, selectively inhibiting the SNr projection to the BGMT biased licking responses to the ipsilateral direction. Our observations broadly support classic BG models and further suggests that ascending basal ganglia output to the thalamus and cortex helps to shape the preparation and initiation of sensory guided movement.
Footnotes
Author contributions: A.M., P.B., C.W., G.S., and D.J. designed research; A.M., P.C., and C.B. trained mice and performed optogenetic experiments; A.M. analyzed data; A.M. and D.J. wrote the paper.
This work was supported by the NIH/National Institute of Neurological Disorders and Stroke (NINDS) Brain Initiative Grant U01NS094302 (DJ), T32 Training Grant 5T32HD071845 (AM), NIH F31 NRSA NS098691 (PB), and DFG Fellowship GZ: WA 3862/1-1 (CW).