title: Dopamine-dependent corticostriatal synaptic filtering regulates sensorimotor behavior.
abstract: Modulation of corticostriatal synaptic activity by dopamine is required for normal sensorimotor behaviors. After loss of nigrostriatal dopamine axons in Parkinson's disease, l-3,4-dihydroxyphenlalanine (l-DOPA) and dopamine D2-like receptor agonists are used as replacement therapy, although these drugs also trigger sensitized sensorimotor responses including dyskinesias and impulse control disorders. In mice, we lesioned dopamine projections to the left dorsal striatum and assayed unilateral sensorimotor deficits with the corridor test as well as presynaptic corticostriatal activity with the synaptic vesicle probe, FM1-43. Sham-lesioned mice acquired food equivalently on both sides, while D2 receptor activation filtered the less active corticostriatal terminals, a response that required coincident co-activation of mGlu-R5 metabotropic glutamate and CB1 endocannabinoid receptors. Lesioned mice did not acquire food from their right, but overused that side following treatment with l-DOPA. Synaptic filtering on the lesioned side was abolished by either l-DOPA or a D2 receptor agonist, but when combined with a CB1 receptor antagonist, l-DOPA or D2 agonists normalized both synaptic filtering and behavior. Thus, high-pass filtering of corticostriatal synapses by the coordinated activation of D2, mGlu-R5, and CB1 receptors is required for normal sensorimotor response to environmental cues.
authors: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors: M Y
authors: MY
authors: Wong
authors: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors: A
authors: A
authors: Borgkvist
authors: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors: S J
authors: SJ
authors: Choi
authors: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors: E V
authors: EV
authors: Mosharov
authors: Departments of Neurology, Pediatrics and Psychology, University of Washington and Seattle Children's Hospital, Seattle, WA 98105, USA.
authors: N S
authors: NS
authors: Bamford
authors: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA; Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10032, USA; Department of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: ds43@cumc.columbia.edu.
authors: D
authors: D
authors: Sulzer
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D015259:Dopamine Agents; C578936:Grm5 protein, mouse; D043884:Receptor, Cannabinoid, CB1; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine
keywords: Parkinson’s; corticostriatal; dopamine; l-DOPA; synapses
references: Eur J Pharmacol. 1989 Mar 21;162(2):329-35
references: 2566500
references: J Neurochem. 1990 Jul;55(1):31-8
references: 2355224
references: J Neurosci. 1990 Jul;10(7):2318-29
references: 1973947
references: Prog Neurobiol. 1991;36(2):93-130
references: 1847748
references: Neuropharmacology. 1991 Mar;30(3):237-44
references: 1649415
references: Brain Res. 1991 May 3;547(2):267-74
references: 1909204
references: J Neurophysiol. 1994 Jan;71(1):17-32
references: 8158226
references: Neuroscience. 1994 Mar;59(2):401-15
references: 7516500
references: Neuroscience. 1995 Apr;65(3):709-30
references: 7609871
references: Neurodegeneration. 1995 Jun;4(2):131-7
references: 7583676
references: Brain Res. 1995 Sep 4;690(2):264-8
references: 8535848
references: Cell. 1995 Dec 29;83(7):1197-209
references: 8548806
references: J Neurosci. 1996 Jan 15;16(2):436-47
references: 8551328
references: Nature. 1996 Feb 1;379(6564):449-51
references: 8559249
references: Eur J Pharmacol. 1996 Jul 4;307(3):331-8
references: 8836622
references: J Neurophysiol. 1997 Apr;77(4):1697-715
references: 9114230
references: J Neurosci. 1997 Jul 15;17(14):5327-33
references: 9204917
references: J Neurochem. 1997 Sep;69(3):1131-7
references: 9282935
references: Prog Neurobiol. 2009 Jan 12;87(1):1-9
references: 18938208
references: J Neurosci. 2009 Feb 25;29(8):2414-27
references: 19244517
references: Neuron. 2009 Aug 13;63(3):372-85
references: 19679076
references: Annu Rev Pharmacol Toxicol. 2010;50:295-322
references: 20055706
references: Brain Res. 1972 Aug 25;43(2):601-5
references: 4340836
references: Life Sci. 1997;61(14):PL 191-7
references: 9335234
references: Eur J Neurosci. 1998 Aug;10(8):2694-706
references: 9767399
references: Nat Neurosci. 1999 Apr;2(4):358-63
references: 10204543
references: Wien Klin Wochenschr. 1961 Nov 10;73:787-8
references: 13869404
references: J Physiol. 2005 Jan 1;562(Pt 1):245-56
references: 15498813
references: NeuroRx. 2004 Jan;1(1):139-54
references: 15717014
references: J Neurol. 2005 Oct;252 Suppl 4:IV37-IV42
references: 16222436
references: Brain Res Bull. 2005 Dec 15;68(1-2):24-30
references: 16325001
references: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8251-6
references: 16698932
references: J Pharmacol Exp Ther. 2006 Jul;318(1):304-11
references: 16569753
references: AAPS J. 2006;8(2):E298-306
references: 16796380
references: J Neurophysiol. 2006 Aug;96(2):512-21
references: 16835359
references: Neuron. 2006 Oct 19;52(2):359-69
references: 17046697
references: J Neurosci Methods. 2007 Jan 30;159(2):224-35
references: 16899300
references: J Neurosci Methods. 2007 May 15;162(1-2):237-43
references: 17346799
references: Neuron. 2008 Apr 10;58(1):89-103
references: 18400166
references: Curr Protoc Neurosci. 2007 Oct;Chapter 9:Unit 9.25
references: 18428668
references: Eur J Neurosci. 2009 Jan;29(1):32-41
references: 19120438
references: Eur J Neurosci. 2010 Jan;31(1):14-28
references: 20092552
references: Eur J Neurosci. 2010 Jun;31(12):2266-78
references: 20529122
references: Nature. 2010 Jul 29;466(7306):622-6
references: 20613723
references: Neuropharmacology. 2011 Jun;60(7-8):1017-41
references: 21036182
references: J Neurosci. 2011 Jun 29;31(26):9563-73
references: 21715621
references: Curr Opin Neurol. 2011 Aug;24(4):324-30
references: 21725242
references: Methods Mol Biol. 2011;793:363-76
references: 21913113
references: Neuron. 2012 Apr 26;74(2):277-84
references: 22542182
references: Neuron. 1999 Dec;24(4):809-17
references: 10624945
references: Rev Neurosci. 2000;11(2-3):159-212
references: 10718152
references: Ann Neurol. 2000 Apr;47(4 Suppl 1):S2-9; discussion S9-11
references: 10762127
references: J Neurosci. 2000 May 1;20(9):3401-7
references: 10777802
references: J Neurophysiol. 2001 Jan;85(1):468-71
references: 11152748
references: J Neurophysiol. 2001 Feb;85(2):659-70
references: 11160501
references: Neuropharmacology. 2001 Jun;40(7):918-26
references: 11378162
references: Nat Neurosci. 2001 Jul;4(7):711-7
references: 11426227
references: J Neural Transm (Vienna). 2001;108(5):559-70
references: 11459076
references: Synapse. 2001 Oct;42(1):54-61
references: 11668591
references: J Neurophysiol. 2013 Nov;110(10):2325-36
references: 23966676
references: Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4578-83
references: 24599591
references: Nature. 2014 Jul 17;511(7509):348-52
references: 24896183
references: Science. 2014 Sep 26;345(6204):1616-20
references: 25258080
references: Eur J Neurosci. 2003 Sep;18(6):1607-14
references: 14511339
references: J Neurochem. 2003 Oct;87(2):273-89
references: 14511105
references: J Neurosci. 2003 Nov 19;23(33):10585-92
references: 14627643
references: Neuron. 2004 May 27;42(4):653-63
references: 15157425
references: J Physiol. 2012 Aug 15;590(16):3743-69
references: 22586226
references: Neurodegener Dis. 2013;11(2):63-71
references: 23038208
references: Mov Disord. 2013 Jan;28(1):41-50
references: 22791686
references: Nature. 2013 Feb 14;494(7436):238-42
references: 23354054
references: J Neurosci. 2013 Jun 19;33(25):10405-26
references: 23785153
references: Mov Disord. 2013 Jul;28(8):1058-63
references: 23389938
references: Neurobiol Dis. 2014 Nov;71:334-44
references: 25171793
references: Trends Neurosci. 2014 Nov;37(11):663-73
references: 25160683
references: J Comp Neurol. 2002 Jan 21;442(4):392-404
references: 11793342
references: J Neurosci. 2002 Apr 1;22(7):2541-9
references: 11923419
references: J Neurosci. 2002 Aug 15;22(16):6900-7
references: 12177188
references: Nat Med. 2003 Jan;9(1):76-81
references: 12461523
references: Tohoku J Exp Med. 2003 Mar;199(3):149-59
references: 12703659
references: J Neurosci. 2003 Aug 20;23(20):7659-69
references: 12930805
references: J Neurosci. 2004 Oct 27;24(43):9541-52
references: 15509741
references: Eur J Pharmacol. 1968 Dec;5(1):107-10
references: 5718510
references: Neuropharmacology. 1978 Jun;17(6):349-53
references: 566861
references: J Comp Neurol. 1987 Sep 22;263(4):567-80
references: 2822779
references: J Pharmacol Exp Ther. 1988 Nov;247(2):680-4
references: 2903237