{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:59Z","timestamp":1785435779583,"version":"3.56.0"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Young Talent Funding (Nachwuchsf\u00f6rderung) of the Faculty of Veterinary Medicine, University Leipzig"},{"id":[{"id":"https:\/\/ror.org\/03s7gtk40","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["SBF 1270\/1,2-299150580"],"award-info":[{"award-number":["SBF 1270\/1,2-299150580"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SBF 1270\/1,2-299150580"],"award-info":[{"award-number":["SBF 1270\/1,2-299150580"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurochemical imbalances in the striatum are thought to contribute to the pathophysiology of DYT1 dystonia (TOR1A), a severe movement disorder. Parvalbumin-positive GABAergic fast-spiking interneurons (PV+ FSI) exert a powerful inhibition within the striatal microcircuitry. To elucidate the impact of PV+ FSI on striatal neurotransmitter dynamics in a DYT1 knock-in (KI) mouse model, we combined optogenetic inhibition of PV+ FSI with in vivo microdialysis (optodialysis) and LC-MS\/MS analysis. Dialysates were collected across baseline (light off), stimulation (light on, 595 nm), and post-stimulation (light off) periods. Basal extracellular concentrations of several analytes, including GABA, dopamine, and adenosine, showed no significant differences between wild-type (WT) and DYT1 KI mice. In WT mice, PV+ FSI inhibition decreased GABA and adenosine levels. In contrast, DYT1 KI mice showed no change in GABA and only a delayed reduction in adenosine post-stimulation. Dopamine, choline, or 5-HIAA were largely unaffected by optogenetic inhibition, with the exception of a genotype-specific reduction of 5-HIAA in the post-stimulation period. These findings suggest impaired inhibitory and neuromodulatory control in the DYT1 KI mice, potentially reflecting compensatory circuit adaptations. The results provide novel insights into striatal microcircuit function in DYT1 dystonia, establish a basis for exploring circuit-level alterations in other movement disorders, and may inform future therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27104530","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"4530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optogenetic Inhibition of Striatal Parvalbuminergic Interneurons Unmasks Impaired GABA and Adenosine Signaling in DYT1 Knock-In Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Jakob","family":"Marx","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susen","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8723-4405","authenticated-orcid":false,"given":"Lisa","family":"H\u00f6fert","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Hochheim","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-4127","authenticated-orcid":false,"given":"Christin","family":"Helmschrodt","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Dre\u00dfler","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and classification of dystonia: A consensus update","volume":"28","author":"Albanese","year":"2013","journal-title":"Mov. 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