Distinct modes of dopamine modulation on striatopallidal synaptic transmission.
2026-04-03, Nature Communications (10.1038/s41467-026-71426-8) (online)C Justin Lee, Yulong Li, Kyungjae Myung, Jae-Ick Kim, Youngeun Lee, Ki Jung Kim, Christian Luscher, Maria Reva, Hyun-Jin Kim, Yemin Kim, Eunjeong Cho, Minseok Jeong, Youngjong Kwak, Seung Eun Lee, and Dong Pyo Jang (?)
Dopamine affects voluntary movement by modulating basal ganglia function. However, the contribution of dopamine on striatopallidal synapses, an initial hub in the indirect pathway connecting the striatum to the GPe, remains poorly understood because of the sparse dopaminergic innervation. Here, we combine optogenetic projection targeting, whole cell patch clamp recordings in acute brain slices from mice, and computational modeling to overcome this limitation. We show that dopamine activates D2 receptors (D2Rs) and D4 receptors (D4Rs) differentially in distinct GPe subregions. In a pinwheel-like fashion, dorsolateral and ventromedial GPe expresses high levels of D2Rs, which exert presynaptic inhibition, while in dorsomedial and ventrolateral GPe D4Rs cause postsynaptic inhibition. Dopamine depletion by 6-OHDA reshapes the region-specific effect of dopamine, shifting it in the opposite direction and contributing to hypokinesia. These findings reveal the mechanism by which the different modality information conveyed spatially through the indirect pathway is differentially modulated by dopamine at striatopallidal synapses.



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