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The tail striatum (TS) is a poorly understood striatal domain with predominantly sensory functions. Recent evidence supports that abnormal TS dopamine transmission in dopaminergic disease contributes to sensory symptoms by dysregulating TS medium spiny neurons (MSNs). Importantly, the ventral TS is segregated into medial, intermediate and lateral divisions in which TS\u2010MSNs express D1 and D2 dopamine receptors unevenly, but the functional significance of this is unclear. We aimed to gain insight into the functional significance of this organisation and to investigate how TS\u2010MSNs are modulated by dopamine. We used whole\u2010cell patch clamping in rat (P45\u201355, both sexes) brain slices to conduct the first in\u2010depth electrophysiological characterisation of TS\u2010MSNs and compared them across divisions. The adjacent dorsolateral striatum (DLS) was included for comparison. We also investigated how bath\u2010applied dopamine and selective dopamine agonists SKF38393 and quinpirole modulate MSNs in each region. We found that TS\u2010MSNs are electrophysiologically distinct from DLS\u2010MSNs, reflecting the established functional differences between these domains. TS\u2010MSNs were more depolarised than DLS\u2010MSNs at rest and had lower rheobase. We also identified functional heterogeneity across the TS divisions. The intermediate division had higher rheobase than the medial or lateral divisions. At rheobase, lateral division TS\u2010MSNs showed higher firing frequencies than medial or intermediate division TS\u2010MSNs. Finally, TS\u2010MSNs showed weaker modulation by dopamine, SKF38393 and quinpirole than DLS\u2010MSNs, which was also uneven across divisions. These data provide a novel electrophysiological characterisation of TS\u2010MSNs, showing they are functionally distinct from DLS\u2010MSNs and heterogeneous across divisions, which could have implications for dopaminergic diseases.<\/jats:p>","DOI":"10.1113\/ep094001","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:18:15Z","timestamp":1787300295000},"page":"4827-4851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct electrophysiology and dopaminergic modulation of medium spiny neurons across divisions of the tail striatum and the dorsolateral striatum"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2201-3367","authenticated-orcid":false,"given":"Bronwyn","family":"Riley","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke E.","family":"Hallum","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical and Mechatronics Engineering The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdjan M.","family":"Vlajkovic","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Freestone","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90094-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60580"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13784"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.12.062"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00290"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012656975-9\/50008-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1993.69.6.1865"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870526"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.5.2204"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/93.3.491"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00754.2001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.007"},{"key":"e_1_2_10_15_1","first-page":"47","article-title":"The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: Old fashioned, but still in vogue","volume":"5","author":"Brisch R.","year":"2014","journal-title":"Frontiers in Psychiatry"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90138-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00766.2001"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90239-9"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300220"},{"issue":"3","key":"e_1_2_10_20_1","article-title":"Whole\u2010cell patch clamp and extracellular electrophysiology recordings in mouse brain slices","volume":"6","author":"Chen H.","year":"2025","journal-title":"Structured, Transparent, Accessible, Reproducible Protocols"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"6","article-title":"The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation","volume":"21","author":"Chicco D.","year":"2020","journal-title":"BioMed Central Genomics"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1412897"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.150029"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1525\/ae.2004.31.4.475"},{"key":"e_1_2_10_25_1","volume-title":"Pattern classification","author":"Duda R. 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