TY - JOUR
T1 - Striatal direct pathway targets Npas1+pallidal neurons
AU - Cui, Qiaoling
AU - Du, Xixun
AU - Chang, Isaac Y.M.
AU - Pamukcu, Arin
AU - Lilascharoen, Varoth
AU - Berceau, Brianna L.
AU - García, Daniela
AU - Hong, Darius
AU - Chon, Uree
AU - Narayanan, Ahana
AU - Kim, Yongsoo
AU - Lim, Byung Kook
AU - Chan, C. Savio
N1 - Publisher Copyright:
Copyright © 2021 the authors.
PY - 2021/5/5
Y1 - 2021/5/5
N2 - The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and their roles in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting response of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson's disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLS dSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson's disease that has not been previously considered. In sum, our results suggest that dSPN input to the GPe is a critical circuit component that is involved in the regulation of movement in both healthy and parkinsonian states.
AB - The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and their roles in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting response of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson's disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLS dSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson's disease that has not been previously considered. In sum, our results suggest that dSPN input to the GPe is a critical circuit component that is involved in the regulation of movement in both healthy and parkinsonian states.
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U2 - 10.1523/JNEUROSCI.2306-20.2021
DO - 10.1523/JNEUROSCI.2306-20.2021
M3 - Article
C2 - 33731445
AN - SCOPUS:85105062913
SN - 0270-6474
VL - 41
SP - 3966
EP - 3987
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 18
ER -