Age-dependent regulation of synaptic connections by dopamine D2 receptors

Nature Neuroscience
Jie-Min JiaZheng Li

Abstract

Dopamine D2 receptors (D2R) are G protein-coupled receptors that modulate synaptic transmission and are important for various brain functions, including learning and working memory. Abnormal D2R signaling has been implicated in psychiatric disorders such as schizophrenia. Here we report a new function of D2R in dendritic spine morphogenesis. Activation of D2R reduced spine number via GluN2B- and cAMP-dependent mechanisms in mice. Notably, this regulation occurred only during adolescence. During this period, D2R overactivation caused by mutations in the schizophrenia risk gene Dtnbp1 led to spine deficiency, dysconnectivity in the entorhinal-hippocampal circuit and impairment of spatial working memory. Notably, these defects could be ameliorated by D2R blockers administered during adolescence. Our findings suggest an age-dependent function of D2R in spine development, provide evidence that D2R dysfunction during adolescence impairs neuronal circuits and working memory, and indicate that adolescent interventions to prevent aberrant D2R activity protect against cognitive impairment.

References

Apr 1, 1970·The American Journal of Anatomy·A Peters, I R Kaiserman-Abramof
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·J DragoS P Huang
Nov 1, 1995·Neurobiology of Learning and Memory·Y H Cho, R Jaffard
Oct 15, 1998·Journal of Neurology, Neurosurgery, and Psychiatry·L J GareyS R Hirsch
Jul 8, 1999·Current Opinion in Neurobiology·K M Harris
Jan 13, 2000·Archives of General Psychiatry·L A Glantz, D A Lewis
Jun 8, 2002·Annual Review of Neuroscience·David A Lewis, Pat Levitt
Nov 20, 2003·Nature Reviews. Molecular Cell Biology·Zheng Li, Morgan Sheng
Jan 7, 2004·Nature Reviews. Neuroscience·Rafael Yuste, Tobias Bonhoeffer
Jun 4, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kuei Y Tseng, Patricio O'Donnell
Jun 3, 2005·The American Journal of Psychiatry·Nutan KolluriDavid A Lewis
Aug 2, 2005·Neuron·Antonello Bonci, F Woodward Hopf
Dec 13, 2005·Journal of Neurochemistry·Kerstin HåkanssonGilberto Fisone
Jan 24, 2006·Biological Psychiatry·Klaas E StephanKarl J Friston
Oct 4, 2006·Trends in Cognitive Sciences·Michael E Hasselmo, Chantal E Stern
Dec 6, 2006·Neuron·Xian-Yu LiuJohn Q Wang
Apr 5, 2007·Nature Protocols·John A O'Brien, Sarah C R Lummis
Aug 25, 2007·Annual Review of Clinical Psychology·Michael F Green
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yukihiko IizukaRichard E Straub
Feb 21, 2008·Annual Review of Neuroscience·Jennifer N Bourne, Kristen M Harris
May 28, 2008·The Journal of Cell Biology·Xiao-Wei ChenZhuan Zhou
Mar 28, 2009·Schizophrenia Bulletin·Oliver D Howes, Shitij Kapur
Sep 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hervé FiorentinoJean-Luc Gaiarsa
Oct 2, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gregory Z Tau, Bradley S Peterson
Nov 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yuanyuan JiBai Lu
Dec 17, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yan-Chun LiWen-Jun Gao
Jan 1, 2009·Progress in Brain Research·Konrad Talbot
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Mar 23, 2011·Current Opinion in Pharmacology·H Y Meltzer, B W Massey
Apr 15, 2011·Nature·Kristen J BrennandFred H Gage
Nov 26, 2011·The Journal of Experimental Biology·Michael P WilkieLeslie T Buck
Dec 17, 2011·Annals of the New York Academy of Sciences·Lawrence ChanHideto Kojima
Apr 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Heidrun SchultzJan Peters

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Citations

Dec 10, 2013·Biological Psychiatry·Richard M O'Connor, John F Cryan
Aug 20, 2015·Proceedings of the National Academy of Sciences of the United States of America·Paul James BanksZafar Iqbal Bashir
Mar 5, 2016·Nature Reviews. Drug Discovery·Mark J MillanDaniel Weinberger
Jan 24, 2015·Neuroscience and Biobehavioral Reviews·Colm M O'Tuathaigh, John L Waddington
Feb 12, 2015·British Journal of Pharmacology·Jean-Martin BeaulieuRaul R Gainetdinov
Feb 14, 2015·Behavioural Brain Research·Sanjeev K BhardwajNicolas Cermakian
Jun 23, 2015·CNS Spectrums·Monique Ernst, Monica Luciana
Jun 13, 2015·Biological Psychiatry·Yunbok KimBita Moghaddam
Feb 27, 2014·Schizophrenia Research·Anita L PinnerJames H Meador-Woodruff
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Hirobumi TadaTakuya Takahashi
Mar 1, 2017·Experimental Neurobiology·Suji HamHeh-In Im
Jul 25, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Crystal C Y Leung, Yung H Wong
May 23, 2018·Medicinal Research Reviews·Xu-Feng Huang, Xueqin Song
Dec 30, 2014·World Journal of Psychiatry·Mary V Seeman
Oct 30, 2013·Nature Neuroscience·Dong-Min YinLin Mei
Jan 20, 2018·Nature Communications·Jan RozmanMartin Hrabe de Angelis
Feb 23, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Seol-Ae LeeSang Ki Park
Oct 12, 2018·Journal of Neurogenetics·Alicia MansillaAlberto Ferrús
Feb 13, 2020·Npj Regenerative Medicine·Celia Herrera-RinconMichael Levin
Mar 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Eugenia TomasellaDiego M Gelman
Oct 31, 2018·Frontiers in Neuroscience·Minmin HuXu-Feng Huang
May 17, 2017·Scientific Reports·Yi-Ting ChenHsien-Yuan Lane
Feb 17, 2021·Molecular Psychiatry·Jun ZhaoZheng Li
Feb 4, 2021·Npj Regenerative Medicine·Celia Herrera-RinconMichael Levin

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Methods Mentioned

BETA
transfection
gene knockout
PCR

Software Mentioned

TopScan
Clampex
LSM
Olympus fluoview
Metamorph

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