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Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Recent studies have implicated dopaminergic signaling within the substantia nigra pars reticulata (SNr) in the emergence of Parkinsonian motor deficits. To better understand the mechanisms underlying this dependence, the ability of dopamine to modulate SNr neuron activity was studied in ex vivo mouse brain slices. In addition to presynaptically inhibiting phasic GABA release, D2 dopamine receptor (D2R) signaling unexpectedly suppressed a tonic, GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor\u2013mediated inhibition of SNr neuron spiking. Our studies demonstrated that this tonic modulation was largely mediated by GAT-1\u2013dependent GABA release from ALDH1A1-expressing dopaminergic neurons. In contrast, the ability of D2R agonists to disinhibit SNr neurons depended on D2R-expressing astrocytes and stimulation of GAT-3 uptake of GABA from the extracellular space. In addition to underscoring the importance of dendritically released dopamine in modulating synaptic transmission, our studies demonstrate that dopaminergic modulation of astrocytes plays a key role in modulating SNr circuits and motor behavior.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adq8840","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:47Z","timestamp":1788976727000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-4312","authenticated-orcid":true,"given":"DeNard V.","family":"Simmons","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1378-2545","authenticated-orcid":true,"given":"Oscar Andr\u00e9s","family":"Moreno-Ramos","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA."},{"name":"Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-1500","authenticated-orcid":true,"given":"Divya D. 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