The study investigates the regulation of motor behaviors in Parkinsonian models using optogenetic control of basal ganglia circuitry. The authors used Cre-dependent viral expression of channelrhodopsin-2 (ChR2) in medium spiny projection neurons (MSNs) of the striatum, targeting either the direct or indirect pathways. Bilateral activation of indirect-pathway MSNs induced a parkinsonian state characterized by increased freezing, bradykinesia, and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia, and locomotor initiation. These findings establish a critical role for basal ganglia circuitry in bidirectional regulation of motor behavior and suggest that modulation of direct-pathway circuitry may be an effective therapeutic strategy for improving parkinsonian motor deficits.The study investigates the regulation of motor behaviors in Parkinsonian models using optogenetic control of basal ganglia circuitry. The authors used Cre-dependent viral expression of channelrhodopsin-2 (ChR2) in medium spiny projection neurons (MSNs) of the striatum, targeting either the direct or indirect pathways. Bilateral activation of indirect-pathway MSNs induced a parkinsonian state characterized by increased freezing, bradykinesia, and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia, and locomotor initiation. These findings establish a critical role for basal ganglia circuitry in bidirectional regulation of motor behavior and suggest that modulation of direct-pathway circuitry may be an effective therapeutic strategy for improving parkinsonian motor deficits.