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bioRxiv · 10.1101/2022.05.18.492478

The Indirect Pathway of the Basal Ganglia Promotes Negative Reinforcement, But Not Motor Suppression

Isett, B. R.·Nguyen, K. P.·Schwenk, J. C.·Snyder, C. N.·Adegbesan, K. A.·Ziausyte, U.·Gittis, A. H.
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Abstract

Optogenetic stimulation of Adora2a receptor expressing spiny projection neurons (A2A-SPN) in the striatum drives locomotor suppression and negative reinforcement, results attributed to activation of the indirect pathway. The sole long-range projection target of A2A-SPNs is the external globus pallidus (GPe). Unexpectedly, we found that inhibition of the GPe did not suppress movement, but did drive robust negative reinforcement in a real-time place preference assay. 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 negative reinforcement than in motor control and challenges the assumption that activity of A2A-SPNs is synonymous with indirect pathway activity.

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Isett, B. R., Nguyen, K. P., Schwenk, J. C., Snyder, C. N., Adegbesan, K. A., Ziausyte, U., Gittis, A. H.. 2022-05-19. The Indirect Pathway of the Basal Ganglia Promotes Negative Reinforcement, But Not Motor Suppression. https://doi.org/10.1101/2022.05.18.492478

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