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Myung, Kyungjae
Center for Genomic Integrity
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Two distinct modes of dopaminergic modulation on striatopallidal synaptic transmission in health and diseases

Lee, YoungeunCho, EunjeongKim, Hyun-JinMyung, KyungjaeLi, YulongLee, Seung EunKim, EunjoonKim, Jae-Ick
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Dopamine (DA) and its G-protein-coupled receptors (GPCRs) control willed movement through the D1-direct
pathway and D2-indirect pathway within the basal ganglia. In a classical model, excessive activity in the indirect
pathway is one of the circuit mechanisms underlying parkinsonism. Although striatopallidal synapses serve as a
critical gateway of the indirect pathway, the physiological functions of dopamine on striatopallidal transmission
remain poorly understood. Here, we sought to understand how DA through the nigropallidal pathway modulates
striatopallidal transmission. We found that striatopallidal synapses region-specifically modulate indirect pathway via
directly released dopamine on the GPe. Notably, 6-OHDA-induced DA depletion particularly promotes D2R-mediated
presynaptic inhibition in ventrolateral and dorsomedial subregions of the GPe. To sum up, these results demonstrate
that synaptic information conveyed by the indirect pathway can be differentially regulated by DA via distinct modes of
action in the GPe subregions, which can be determined by anatomical locations of striatopallidal synapses.
Korean Society for Molecular and Cellular Biology


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