Treffer: Computational modelling identifies key determinants of subregion-specific dopamine dynamics in the striatum.
Title:
Computational modelling identifies key determinants of subregion-specific dopamine dynamics in the striatum.
Authors:
Ejdrup A; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Dreyer JK; Department of Bioinformatics, H Lundbeck A/S, Valby, Denmark., Lycas MD; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Jørgensen SH; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Robbins TW; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.; Department of Psychology, University of Cambridge, Cambridge, United Kingdom., Dalley J; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.; Department of Psychology, University of Cambridge, Cambridge, United Kingdom.; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom., Herborg F; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Gether U; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Source:
ELife [Elife] 2026 Jan 23; Vol. 14. Date of Electronic Publication: 2026 Jan 23.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
Imprint Name(s):
Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
MeSH Terms:
References:
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Basal Ganglia. 2016 Aug;6(3):123-148. (PMID: 27141430)
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Nat Neurosci. 2015 Aug;18(8):1084-93. (PMID: 26147533)
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J Biol Chem. 1980 Nov 25;255(22):10909-15. (PMID: 7430162)
Brain Res. 1985 May 6;333(2):325-9. (PMID: 3995298)
J Neurochem. 2003 Dec;87(5):1284-95. (PMID: 14622108)
J Neurosci. 1994 Oct;14(10):6084-93. (PMID: 7931564)
Trends Neurosci. 2007 Feb;30(2):62-9. (PMID: 17173981)
Cell. 2018 Feb 8;172(4):706-718.e15. (PMID: 29398114)
J Neurosci. 2010 Oct 20;30(42):14273-83. (PMID: 20962248)
J Neurochem. 2002 May;81(4):859-69. (PMID: 12065645)
Prog Brain Res. 2000;125:291-302. (PMID: 11098665)
Psychopharmacology (Berl). 2007 Apr;191(3):507-20. (PMID: 17031711)
Cell. 2021 May 13;184(10):2733-2749.e16. (PMID: 33861952)
J Neurosci. 2009 Jan 14;29(2):444-53. (PMID: 19144844)
PLoS Comput Biol. 2020 Nov 30;16(11):e1008410. (PMID: 33253315)
Elife. 2026 Jan 23;14:. (PMID: 41574574)
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2866-71. (PMID: 12604788)
Brain Res Mol Brain Res. 2005 Oct 3;139(2):341-7. (PMID: 16051392)
Nature. 2021 Feb;590(7846):451-456. (PMID: 33361810)
ACS Chem Neurosci. 2015 Nov 18;6(11):1802-12. (PMID: 26322962)
Neurobiol Dis. 2020 Feb;134:104666. (PMID: 31682992)
J Neurochem. 2014 Nov;131(3):348-55. (PMID: 24988947)
J Biol Chem. 2021 Dec;297(6):101361. (PMID: 34756883)
Neurochem Int. 2012 Dec;61(7):986-91. (PMID: 22819794)
Nature. 2013 Aug 29;500(7464):575-9. (PMID: 23913271)
J Neurosci. 2010 Jun 16;30(24):8229-33. (PMID: 20554874)
Curr Protoc Neurosci. 2009 Apr;Chapter 7:Unit7.1. (PMID: 19340812)
J Neurochem. 2009 Mar;108(6):1575-84. (PMID: 19183252)
Nat Neurosci. 2024 Apr;27(4):737-746. (PMID: 38321294)
Science. 2022 Mar 25;375(6587):1378-1385. (PMID: 35324301)
J Neurophysiol. 1991 Feb;65(2):264-72. (PMID: 2016641)
Elife. 2020 Feb 11;9:. (PMID: 32043970)
Nat Neurosci. 2018 Jun;21(6):787-793. (PMID: 29760524)
Mol Pharmacol. 1976 Sep;12(5):800-12. (PMID: 995128)
ACS Chem Neurosci. 2015 Sep 16;6(9):1509-16. (PMID: 25062330)
J Neurochem. 2010 Apr;113(1):27-41. (PMID: 20085610)
Nature. 2023 Feb;614(7946):108-117. (PMID: 36653449)
J Neurosci. 2015 Sep 16;35(37):12845-58. (PMID: 26377471)
J Biol Chem. 2020 Apr 17;295(16):5229-5244. (PMID: 32132171)
Eur J Pharmacol. 1992 Mar 3;212(2-3):263-6. (PMID: 1601069)
Pharmacol Rev. 2011 Sep;63(3):585-640. (PMID: 21752877)
Neuropsychopharmacology. 2021 Nov;46(12):2043-2047. (PMID: 33603136)
Nat Neurosci. 2016 Jan;19(1):117-26. (PMID: 26595651)
J Neurosci. 2020 Apr 1;40(14):2868-2881. (PMID: 32071139)
Neurochem Int. 2019 Feb;123:13-21. (PMID: 30179648)
J Neurosci. 2001 Aug 15;21(16):6338-47. (PMID: 11487657)
Signal Transduct Target Ther. 2024 Apr 10;9(1):88. (PMID: 38594257)
Cell Rep. 2022 Sep 27;40(13):111431. (PMID: 36170827)
Nat Neurosci. 2016 Apr;19(4):578-86. (PMID: 26900925)
ACS Chem Neurosci. 2019 Aug 21;10(8):3419-3426. (PMID: 31361457)
Eur J Neurosci. 2011 Dec;34(12):1997-2006. (PMID: 22122410)
J Neurosci. 1994 Jan;14(1):442-50. (PMID: 8283249)
Basal Ganglia. 2016 Aug;6(3):123-148. (PMID: 27141430)
Opt Nanoscopy. 2012;1(6):. (PMID: 25431749)
Neuropsychopharmacology. 2004 Oct;29(10):1790-9. (PMID: 15226739)
J Neurosci. 2010 Mar 3;30(9):3398-408. (PMID: 20203199)
J Pharmacol Exp Ther. 1992 Sep;262(3):1085-94. (PMID: 1527715)
Neuroscience. 1994 Oct;62(3):641-5. (PMID: 7870295)
Nat Commun. 2017 Sep 29;8(1):740. (PMID: 28963530)
Nature. 2016 Jul 28;535(7613):505-10. (PMID: 27398617)
J Neurosci. 2016 Jan 06;36(1):98-112. (PMID: 26740653)
ACS Chem Neurosci. 2016 Jul 20;7(7):941-51. (PMID: 27124386)
Elife. 2023 Jun 05;12:. (PMID: 37272423)
J Neurophysiol. 1995 Sep;74(3):1137-48. (PMID: 7500139)
Neuron. 2019 May 22;102(4):786-800.e5. (PMID: 31003725)
EJNMMI Res. 2019 Sep 18;9(1):92. (PMID: 31535286)
Brain Res. 1974 Dec 27;82(2):341-8. (PMID: 4374297)
Ann N Y Acad Sci. 2007 May;1104:192-212. (PMID: 17416920)
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2180-8. (PMID: 27001837)
Brain Res. 1972 Sep 15;44(1):283-8. (PMID: 4403485)
J Neurosci. 1998 Jun 1;18(11):4106-18. (PMID: 9592091)
Nat Neurosci. 2001 Dec;4(12):1224-9. (PMID: 11713470)
Trends Neurosci. 2004 May;27(5):270-7. (PMID: 15111009)
FASEB J. 2021 Aug;35(8):e21791. (PMID: 34320240)
Anal Chem. 2002 Feb 1;74(3):539-46. (PMID: 11838672)
Annu Rev Neurosci. 2019 Jul 8;42:459-483. (PMID: 31018098)
ACS Chem Neurosci. 2023 May 3;14(9):1622-1630. (PMID: 37043174)
Biochem Pharmacol. 1979 Dec 15;28(24):3617-27. (PMID: 533562)
Mol Cell Biochem. 1982 Mar 19;43(2):65-80. (PMID: 6123940)
Biophys J. 1995 May;68(5):1699-715. (PMID: 7612814)
J Physiol. 1981 Dec;321:225-57. (PMID: 7338810)
Med Res Rev. 1995 Jan;15(1):33-45. (PMID: 7898168)
J Neurochem. 1989 Sep;53(3):898-906. (PMID: 2527290)
Rev Neurosci. 2000;11(2-3):159-212. (PMID: 10718152)
Trends Neurosci. 2023 Mar;46(3):228-239. (PMID: 36635111)
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):E2751-9. (PMID: 24979798)
J Neurosci. 2009 May 27;29(21):6794-808. (PMID: 19474307)
ACS Chem Neurosci. 2017 Oct 18;8(10):2275-2289. (PMID: 28714693)
Neuropsychopharmacology. 2010 Feb;35(3):641-55. (PMID: 19890265)
Neuroscience. 1986 Oct;19(2):427-45. (PMID: 3095678)
Nat Commun. 2023 Sep 22;14(1):5915. (PMID: 37739964)
J Neurophysiol. 2013 Jan;109(1):171-82. (PMID: 23054599)
Nature. 2025 Jul;643(8074):1333-1342. (PMID: 40369067)
Int J Mol Sci. 2021 Apr 15;22(8):. (PMID: 33920848)
Annu Rev Neurosci. 2007;30:259-88. (PMID: 17600522)
Nat Neurosci. 2004 Apr;7(4):341-6. (PMID: 14990933)
J Neurosci. 2001 May 1;21(9):RC141: 1-4. (PMID: 11312315)
Cell Rep. 2022 Oct 11;41(2):111470. (PMID: 36223748)
J Biol Chem. 2023 Feb;299(2):102900. (PMID: 36640864)
Front Synaptic Neurosci. 2018 Jul 10;10:20. (PMID: 30042672)
Nat Commun. 2023 Oct 27;14(1):6852. (PMID: 37891198)
Proc Natl Acad Sci U S A. 2023 Feb 14;120(7):e2215230120. (PMID: 36749722)
ACS Chem Neurosci. 2010 Mar 17;1(3):234-245. (PMID: 20368748)
Nat Rev Neurosci. 2021 Jun;22(6):345-358. (PMID: 33837376)
Nat Neurosci. 2015 Aug;18(8):1084-93. (PMID: 26147533)
Trends Neurosci. 2007 May;30(5):220-7. (PMID: 17400299)
Z Zellforsch Mikrosk Anat. 1968;91(1):1-74. (PMID: 5724812)
J Biol Chem. 1980 Nov 25;255(22):10909-15. (PMID: 7430162)
Brain Res. 1985 May 6;333(2):325-9. (PMID: 3995298)
J Neurochem. 2003 Dec;87(5):1284-95. (PMID: 14622108)
J Neurosci. 1994 Oct;14(10):6084-93. (PMID: 7931564)
Trends Neurosci. 2007 Feb;30(2):62-9. (PMID: 17173981)
Cell. 2018 Feb 8;172(4):706-718.e15. (PMID: 29398114)
J Neurosci. 2010 Oct 20;30(42):14273-83. (PMID: 20962248)
J Neurochem. 2002 May;81(4):859-69. (PMID: 12065645)
Prog Brain Res. 2000;125:291-302. (PMID: 11098665)
Psychopharmacology (Berl). 2007 Apr;191(3):507-20. (PMID: 17031711)
Cell. 2021 May 13;184(10):2733-2749.e16. (PMID: 33861952)
J Neurosci. 2009 Jan 14;29(2):444-53. (PMID: 19144844)
PLoS Comput Biol. 2020 Nov 30;16(11):e1008410. (PMID: 33253315)
Elife. 2026 Jan 23;14:. (PMID: 41574574)
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2866-71. (PMID: 12604788)
Brain Res Mol Brain Res. 2005 Oct 3;139(2):341-7. (PMID: 16051392)
Nature. 2021 Feb;590(7846):451-456. (PMID: 33361810)
ACS Chem Neurosci. 2015 Nov 18;6(11):1802-12. (PMID: 26322962)
Neurobiol Dis. 2020 Feb;134:104666. (PMID: 31682992)
J Neurochem. 2014 Nov;131(3):348-55. (PMID: 24988947)
J Biol Chem. 2021 Dec;297(6):101361. (PMID: 34756883)
Neurochem Int. 2012 Dec;61(7):986-91. (PMID: 22819794)
Nature. 2013 Aug 29;500(7464):575-9. (PMID: 23913271)
J Neurosci. 2010 Jun 16;30(24):8229-33. (PMID: 20554874)
Curr Protoc Neurosci. 2009 Apr;Chapter 7:Unit7.1. (PMID: 19340812)
J Neurochem. 2009 Mar;108(6):1575-84. (PMID: 19183252)
Nat Neurosci. 2024 Apr;27(4):737-746. (PMID: 38321294)
Science. 2022 Mar 25;375(6587):1378-1385. (PMID: 35324301)
J Neurophysiol. 1991 Feb;65(2):264-72. (PMID: 2016641)
Elife. 2020 Feb 11;9:. (PMID: 32043970)
Nat Neurosci. 2018 Jun;21(6):787-793. (PMID: 29760524)
Mol Pharmacol. 1976 Sep;12(5):800-12. (PMID: 995128)
ACS Chem Neurosci. 2015 Sep 16;6(9):1509-16. (PMID: 25062330)
J Neurochem. 2010 Apr;113(1):27-41. (PMID: 20085610)
Nature. 2023 Feb;614(7946):108-117. (PMID: 36653449)
J Neurosci. 2015 Sep 16;35(37):12845-58. (PMID: 26377471)
J Biol Chem. 2020 Apr 17;295(16):5229-5244. (PMID: 32132171)
Eur J Pharmacol. 1992 Mar 3;212(2-3):263-6. (PMID: 1601069)
Pharmacol Rev. 2011 Sep;63(3):585-640. (PMID: 21752877)
Neuropsychopharmacology. 2021 Nov;46(12):2043-2047. (PMID: 33603136)
Nat Neurosci. 2016 Jan;19(1):117-26. (PMID: 26595651)
J Neurosci. 2020 Apr 1;40(14):2868-2881. (PMID: 32071139)
Neurochem Int. 2019 Feb;123:13-21. (PMID: 30179648)
J Neurosci. 2001 Aug 15;21(16):6338-47. (PMID: 11487657)
Signal Transduct Target Ther. 2024 Apr 10;9(1):88. (PMID: 38594257)
Cell Rep. 2022 Sep 27;40(13):111431. (PMID: 36170827)
Nat Neurosci. 2016 Apr;19(4):578-86. (PMID: 26900925)
ACS Chem Neurosci. 2019 Aug 21;10(8):3419-3426. (PMID: 31361457)
Eur J Neurosci. 2011 Dec;34(12):1997-2006. (PMID: 22122410)
J Neurosci. 1994 Jan;14(1):442-50. (PMID: 8283249)
Grant Information:
R266-2017-4331 Lundbeck Foundation; R276-2018-792 Lundbeck Foundation; R359-2020-2301 Lundbeck Foundation; R181-2014-3090 Lundbeck Foundation; R303-2018-3540 Lundbeck Foundation; NNF24OC0088870 The Novo Nordisk Foundation
Contributed Indexing:
Keywords: computational biology; dopamine; dopamine receptors; dopamine transporter; mouse; neuroscience; phasic versus tonic release; striatum; systems biology; three-dimensional computational model
Substance Nomenclature:
VTD58H1Z2X (Dopamine)
0 (Dopamine Plasma Membrane Transport Proteins)
0 (Receptors, Dopamine D2)
0 (Receptors, Dopamine D1)
0 (Dopamine Plasma Membrane Transport Proteins)
0 (Receptors, Dopamine D2)
0 (Receptors, Dopamine D1)
Entry Date(s):
Date Created: 20260123 Date Completed: 20260123 Latest Revision: 20260125
Update Code:
20260125
PubMed Central ID:
PMC12829992
DOI:
10.7554/eLife.105214
PMID:
41574574
Database:
MEDLINE
Weitere Informationen
Striatal dopamine (DA) release regulates reward-related learning and motivation and is believed to consist of a short-lived phasic and continuous tonic component. Here, we build a large-scale three-dimensional model of extracellular DA dynamics in dorsal (DS) and ventral striatum (VS). The model predicts rapid dynamics in DS with little to no basal DA and slower dynamics in the VS enabling build-up of tonic DA levels. These regional differences do not reflect release-related phenomena but rather differential dopamine transporter (DAT) activity. Interestingly, our simulations posit DAT nanoclustering as a possible regulator of this activity. Receptor binding simulations show that D1 receptor occupancy follows extracellular DA concentration with milliseconds delay, while D2 receptors do not respond to brief pauses in firing but rather integrate DA signal over seconds. Summarised, our model distills recent experimental observations into a computational framework that challenges prevailing paradigms of striatal DA signalling.
(© 2025, Ejdrup et al.)
AE, ML, SJ, TR, JD, FH, UG No competing interests declared, JD is affiliated with H. Lundbeck A/S. The author has no other competing interests to declare