The respective activation and silencing of striatal direct and indirect pathway neurons support behavior encoding

The basal ganglia are notorious for their influence on action control and modulation of movements. Proper organization of neuronal activity within the two efferent pathways of the dorsal striatum, a major input of basal ganglia, is critical for appropriate behavioral control. The classical model of basal ganglia suggests that striatal indirect and direct pathways exert opposite action on the thalamo-cortical activation triggering motor control. Recent studies challenged this view by describing conjoint neuronal activities during action initiation or decision-making. Therefore, additional investigations are needed to clarify the function of these two pathways. In the present work, using large-scale in vivo calcium imaging (Inscopix), we evaluated how direct and indirect pathway striatal projection neurons (SPNs) in the dorsal striatum encode behaviors during self-paced spontaneous exploration of an open-field. We observe that both striatal pathways diverge in their tuning properties to spontaneous behaviors. Using supervised leaning algorithms, we found that direct pathway SPNs encode behaviors through their activation, whereas behavior-relevant SPNs of the indirect pathway are consistently silent. Our findings demonstrate an opposite yet cooperative organization of behaviors encoding within striatal output pathways that solves questions raised by recent correlative studies. Altogether our results generate a new framework to understand striatal physiology and its dysfunction.