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The dorsal striatum contains four main types of spiny projection neurons (SPNs): patch (or striosome) and matrix subtypes of both direct-pathway (dSPNs) and indirect-pathway (iSPNs). Activation of patch dSPNs suppresses locomotion by inhibiting ALDH1A1\u207a DANs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We combined RNAscope in situ hybridization with SPN subtype-specific reporter mice to quantify patch and total dSPNs and iSPNs in\n                      <jats:italic>Pitx3<\/jats:italic>\n                      -deficient and control mice. Three patch SPN reporter lines (\n                      <jats:italic>Kremen1<\/jats:italic>\n                      <jats:sup>2A\u2009\u2212\u2009Cre<\/jats:sup>\n                      ,\n                      <jats:italic>Nr4a1<\/jats:italic>\n                      -\n                      <jats:italic>GFP<\/jats:italic>\n                      , and\n                      <jats:italic>Pdyn<\/jats:italic>\n                      <jats:sup>IRES\u2212Cre<\/jats:sup>\n                      ) were used to map projections. Optogenetic stimulation was performed in freely moving mice to assess the behavioral effects of activating patch dSPNs and iSPNs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pitx3-<\/jats:italic>\n                      deficient mice showed no change in the overall dSPN: iSPN ratio but exhibited a marked shift in the patch dSPN: patch iSPN ratio, which decreased from 1.7 in control mice to 0.7 in the\n                      <jats:italic>Pitx3-<\/jats:italic>\n                      deficient group. Accordingly, patch dSPN projections to the\n                      <jats:italic>substantia nigra pars reticulata<\/jats:italic>\n                      (SNr) were reduced, whereas patch iSPN projections to the\n                      <jats:italic>globus pallidus externus<\/jats:italic>\n                      (GPe) were enhanced. Notably, while optogenetic stimulation of patch dSPNs and iSPNs suppressed locomotion in control mice, the same stimulation promoted locomotion in\n                      <jats:italic>Pitx3<\/jats:italic>\n                      -deficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings reveal a selective reorganization of patch SPNs in response to developmental loss of ALDH1A1\u207a DANs, characterized by reduced patch dSPN and enhanced patch iSPN influence. This shift may underlie the paradoxical hyperlocomotion observed in\n                      <jats:italic>Pitx3<\/jats:italic>\n                      -deficient mice and provides insight into circuit-level adaptations with potential therapeutic relevance for PD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-025-00920-2","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T06:34:10Z","timestamp":1767422050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Developmental dopamine loss rewires striatal circuits to promote locomotion"],"prefix":"10.1186","volume":"21","author":[{"given":"Jie","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breanna T.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M. 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