This study found that optogenetic stimulation of Adora2a receptor-expressing spiny projection neurons (A2A-SPNs) in the striatum can induce locomotor suppression and transient punishment, which is attributed to activation of the indirect pathway. It was also discovered that A2A-SPNs inhibit other SPNs through a short-range inhibitory collateral network in the striatum, and optogenetic stimuli that drive motor suppression utilize this common mechanism.
Optogenetic stimulation of Adora2a receptor-expressing spiny projection neurons (A2A-SPNs) in the stria-tum drives locomotor suppression and transient punishment, results attributed to activation of the indirect pathway. The sole long-range projection target of A2A-SPNs is the external globus pallidus (GPe). Unexpect-edly, we found that inhibition of the GPe drove transient punishment but not suppression of movement. Within the striatum, A2A-SPNs inhibit other SPNs through a short-range inhibitory collateral network, and we found that optogenetic stimuli that drove motor suppression shared a common mechanism of recruiting this inhibitory collateral network. Our results suggest that the indirect pathway plays a more prominent role in transient punishment than in motor control and challenges the assumption that activity of A2A-SPNs is syn-onymous with indirect pathway activity.
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