Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory

Molecular Psychiatry volume 26, pages 6218–6236 (2021)Cite this article

Subjects

Abstract

Exposure to drugs of abuse induces alterations of dendritic spine morphology and density that has been proposed to be a cellular basis of long-lasting addictive memory and heavily depend on remodeling of its underlying actin cytoskeleton by the actin cytoskeleton regulators. However, the actin cytoskeleton regulators involved and the specific mechanisms whereby drugs of abuse alter their expression or function are largely unknown. Twinfilin (Twf1) is a highly conserved actin-depolymerizing factor that regulates actin dynamics in organisms from yeast to mammals. Despite abundant expression of Twf1 in mammalian brain, little is known about its importance for brain functions such as experience-dependent synaptic and behavioral plasticity. Here we show that conditioned morphine withdrawal (CMW)-induced synaptic structure and behavior plasticity depends on downregulation of Twf1 in the amygdala of rats. Genetically manipulating Twf1 expression in the amygdala bidirectionally regulates CMW-induced changes in actin polymerization, spine density and behavior. We further demonstrate that downregulation of Twf1 is due to upregulation of miR101a expression via a previously unrecognized mechanism involving CMW-induced increases in miR101a nuclear processing via phosphorylation of MeCP2 at Ser421. Our findings establish the importance of Twf1 in regulating opioid-induced synaptic and behavioral plasticity and demonstrate its value as a potential therapeutic target for the treatment of opioid addiction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Conditioned morphine withdrawal (CMW) decreased Twf1 expression, increased synaptic actin polymerization in the amygdala, and induced CPA behavior.
Fig. 2: Twf1 negatively regulates actin polymerization, spine density and CPA behavior induced by CMW.
Fig. 3: Overexpression of Twf1 in the amygdala disrupted CMW-induced increase in Arc expression at synapses and reduction of GluR1- and GluR2-containing AMPAR endocytosis.
Fig. 4: Twf1 is a target of miR101a, and inhibition of miR101a function regulates CMW-induced actin polymerization, spine density and CPA behavior.
Fig. 5: CaMKII-dependent phosphorylation of MeCP2 at Ser421 regulated CMW-induced changes in miR101a, Twf1 expression and CPA behavior by attenuating MeCP2 binding to DGCR8.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. Kenny PJ. Brain reward systems and compulsive drug use. Trends Pharm Sci. 2007;28:135–41.

    Article  CAS  PubMed  Google Scholar 

  2. Wise RA, Koob GF. The development and maintenance of drug addiction. Neuropsychopharmacology. 2014;39:254–62.

    Article  PubMed  Google Scholar 

  3. Koob GF. Neurobiology of addiction. Toward the development of new therapies. Ann NY Acad Sci. 2000;909:170–85.

    Article  CAS  PubMed  Google Scholar 

  4. Frenois F, Le Moine C, Cador M. The motivational component of withdrawal in opiate addiction: role of associative learning and aversive memory in opiate addiction from a behavioral, anatomical and functional perspective. Rev Neurosci. 2005;16:255–76.

    Article  CAS  PubMed  Google Scholar 

  5. Milton AL, Everitt BJ. The persistence of maladaptive memory: addiction, drug memories and anti-relapse treatments. Neurosci Biobehav Rev. 2012;36:1119–39.

    Article  PubMed  Google Scholar 

  6. Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K, et al. Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron. 2003;38:447–60.

    Article  CAS  PubMed  Google Scholar 

  7. Stankeviciute NM, Scofield MD, Kalivas PW, Gipson CD. Rapid, transient potentiation of dendritic spines in context-induced relapse to cocaine seeking. Addict Biol. 2014;19:972–4.

    Article  CAS  PubMed  Google Scholar 

  8. Shen HW, Gipson CD, Huits M, Kalivas PW. Prelimbic cortex and ventral tegmental area modulate synaptic plasticity differentially in nucleus accumbens during cocaine-reinstated drug seeking. Neuropsychopharmacology. 2014;39:1169–77.

    Article  CAS  PubMed  Google Scholar 

  9. Hou YY, Lu B, Li M, Liu Y, Chen J, Chi ZQ, et al. Involvement of actin rearrangements within the amygdala and the dorsal hippocampus in aversive memories of drug withdrawal in acute morphine-dependent rats. J Neurosci. 2009;29:12244–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu Y, Zhou QX, Hou YY, Lu B, Yu C, Chen J, et al. Actin polymerization-dependent increase in synaptic Arc/Arg3.1 expression in the amygdala is crucial for the expression of aversive memory associated with drug withdrawal. J Neurosci. 2012;32:12005–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hering H, Sheng M. Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci. 2001;2:880–8.

    Article  CAS  PubMed  Google Scholar 

  12. Cingolani LA, Goda Y. Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci. 2008;9:344–56.

    Article  CAS  PubMed  Google Scholar 

  13. Luo L. Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annu Rev Cell Dev Biol. 2002;18:601–35.

    Article  CAS  PubMed  Google Scholar 

  14. Dillon C, Goda Y. The actin cytoskeleton: integrating form and function at the synapse. Annu Rev Neurosci. 2005;28:25–55.

    Article  CAS  PubMed  Google Scholar 

  15. Bernstein BW, Bamburg JR. ADF/cofilin: a functional node in cell biology. Trends Cell Biol. 2010;20:187–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gu J, Lee CW, Fan Y, Komlos D, Tang X, Sun C, et al. ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nat Neurosci. 2010;13:1208–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Poukkula M, Kremneva E, Serlachius M, Lappalainen P. Actin-depolymerizing factor homology domain: a conserved fold performing diverse roles in cytoskeletal dynamics. Cytoskeleton. 2011;68:471–90.

    Article  CAS  PubMed  Google Scholar 

  18. Goode BL, Drubin DG, Lappalainen P. Regulation of the cortical actin cytoskeleton in budding yeast by twinfilin, a ubiquitous actin monomer-sequestering protein. J Cell Biol. 1998;142:723–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wahlstrom G, Vartiainen M, Yamamoto L, Mattila PK, Lappalainen P, Heino TI. Twinfilin is required for actin-dependent developmental processes in Drosophila. J Cell Biol. 2001;155:787–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Johnston AB, Collins A, Goode BL. High-speed depolymerization at actin filament ends jointly catalysed by Twinfilin and Srv2/CAP. Nat Cell Biol. 2015;17:1504–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vartiainen M, Ojala PJ, Auvinen P, Peranen J, Lappalainen P. Mouse A6/twinfilin is an actin monomer-binding protein that localizes to the regions of rapid actin dynamics. Mol Cell Biol. 2000;20:1772–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang D, Zhang L, Zhao G, Wahlstrom G, Heino TI, Chen J, et al. Drosophila twinfilin is required for cell migration and synaptic endocytosis. J Cell Sci. 2010;123:1546–56.

    Article  CAS  PubMed  Google Scholar 

  23. Yamada S, Uchimura E, Ueda T, Nomura T, Fujita S, Matsumoto K, et al. Identification of twinfilin-2 as a factor involved in neurite outgrowth by RNAi-based screen. Biochem Biophys Res Commun. 2007;363:926–30.

    Article  CAS  PubMed  Google Scholar 

  24. Lamprecht R, LeDoux J. Structural plasticity and memory. Nat Rev Neurosci. 2004;5:45–54.

    Article  CAS  PubMed  Google Scholar 

  25. Ashraf SI, Kunes S. A trace of silence: memory and microRNA at the synapse. Curr Opin Neurobiol. 2006;16:535–9.

    Article  CAS  PubMed  Google Scholar 

  26. Hollander JA, Im HI, Amelio AL, Kocerha J, Bali P, Lu Q, et al. Striatal microRNA controls cocaine intake through CREB signalling. Nature. 2010;466:197–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Im HI, Hollander JA, Bali P, Kenny PJ. MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci. 2010;13:1120–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron. 2007;56:58–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron. 2006;52:255–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cheng TL, Wang Z, Liao Q, Zhu Y, Zhou WH, Xu W, et al. MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Dev Cell. 2014;28:547–60.

    Article  CAS  PubMed  Google Scholar 

  31. Szulwach KE, Li X, Smrt RD, Li Y, Luo Y, Lin L, et al. Cross talk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biol. 2010;189:127–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Q, Song XW, Zou J, Wang GK, Kremneva E, Li XQ, et al. Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy. J Cell Sci. 2010;123:2444–52.

    Article  CAS  PubMed  Google Scholar 

  33. Bockhorn J, Dalton R, Nwachukwu C, Huang S, Prat A, Yee K, et al. MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun. 2013;4:1393.

    Article  PubMed  CAS  Google Scholar 

  34. Urdinguio RG, Fernandez AF, Lopez-Nieva P, Rossi S, Huertas D, Kulis M, et al. Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome. Epigenetics. 2010;5:656–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang W, Ju YY, Zhou QX, Tang JX, Li M, Zhang L, et al. The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC. J Neurosci. 2017;37:7096–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mucha RF, van der Kooy D, O’Shaughnessy M, Bucenieks P. Drug reinforcement studied by the use of place conditioning in rat. Brain Res. 1982;243:91–105.

    Article  CAS  PubMed  Google Scholar 

  37. Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci. 2011;12:623–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen XL, Lu G, Gong YX, Zhao LC, Chen J, Chi ZQ, et al. Expression changes of hippocampal energy metabolism enzymes contribute to behavioural abnormalities during chronic morphine treatment. Cell Res. 2007;17:689–700.

    Article  CAS  PubMed  Google Scholar 

  39. Guo LB, Yu C, Ling QL, Fu Y, Wang YJ, Liu JG. Proteomic analysis of male rat nucleus accumbens, dorsal hippocampus and amygdala on conditioned place aversion induced by morphine withdrawal. Behav Brain Res. 2019;372:112008.

    Article  CAS  PubMed  Google Scholar 

  40. Paavilainen VO, Hellman M, Helfer E, Bovellan M, Annila A, Carlier MF, et al. Structural basis and evolutionary origin of actin filament capping by twinfilin. Proc Natl Acad Sci USA. 2007;104:3113–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bredt DS, Nicoll RA. AMPA receptor trafficking at excitatory synapses. Neuron. 2003;40:361–79.

    Article  CAS  PubMed  Google Scholar 

  42. Anggono V, Huganir RL. Regulation of AMPA receptor trafficking and synaptic plasticity. Curr Opin Neurobiol. 2012;22:461–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Plath N, Ohana O, Dammermann B, Errington ML, Schmitz D, Gross C, et al. Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron. 2006;52:437–44.

    Article  CAS  PubMed  Google Scholar 

  44. Rial Verde EM, Lee-Osbourne J, Worley PF, Malinow R, Cline HT. Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron. 2006;52:461–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  46. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.

    Article  CAS  PubMed  Google Scholar 

  47. Bockhorn J, Yee K, Chang YF, Prat A, Huo D, Nwachukwu C, et al. MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Breast Cancer Res Treat. 2013;137:373–82.

    Article  CAS  PubMed  Google Scholar 

  48. Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, et al. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci USA. 2004;101:360–5.

    Article  CAS  PubMed  Google Scholar 

  49. Elmen J, Lindow M, Silahtaroglu A, Bak M, Christensen M, Lind-Thomsen A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 2008;36:1153–62.

    Article  CAS  PubMed  Google Scholar 

  50. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452:896–9.

    Article  CAS  PubMed  Google Scholar 

  51. Cohen S, Gabel HW, Hemberg M, Hutchinson AN, Sadacca LA, Ebert DH, et al. Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. Neuron. 2011;72:72–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tao J, Hu K, Chang Q, Wu H, Sherman NE, Martinowich K, et al. Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci USA. 2009;106:4882–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature. 2004;432:231–5.

    Article  CAS  PubMed  Google Scholar 

  54. Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setien F, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007;67:1424–9.

    Article  CAS  PubMed  Google Scholar 

  55. Wu H, Tao J, Chen PJ, Shahab A, Ge W, Hart RP, et al. Genome-wide analysis reveals methyl-CpG-binding protein 2-dependent regulation of microRNAs in a mouse model of Rett syndrome. Proc Natl Acad Sci USA. 2010;107:18161–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432:235–40.

    Article  CAS  PubMed  Google Scholar 

  57. Li Y, Kolb B, Robinson TE. The location of persistent amphetamine-induced changes in the density of dendritic spines on medium spiny neurons in the nucleus accumbens and caudate-putamen. Neuropsychopharmacology. 2003;28:1082–5.

    Article  CAS  PubMed  Google Scholar 

  58. Robinson TE, Gorny G, Mitton E, Kolb B. Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex. Synapse. 2001;39:257–66.

    Article  CAS  PubMed  Google Scholar 

  59. Kim CH, Lisman JE. A role of actin filament in synaptic transmission and long-term potentiation. J Neurosci. 1999;19:4314–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zito K, Knott G, Shepherd GM, Shenolikar S, Svoboda K. Induction of spine growth and synapse formation by regulation of the spine actin cytoskeleton. Neuron. 2004;44:321–34.

    Article  CAS  PubMed  Google Scholar 

  61. Helfer E, Nevalainen EM, Naumanen P, Romero S, Didry D, Pantaloni D, et al. Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility. EMBO J. 2006;25:1184–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Vartiainen MK, Sarkkinen EM, Matilainen T, Salminen M, Lappalainen P. Mammals have two twinfilin isoforms whose subcellular localizations and tissue distributions are differentially regulated. J Biol Chem. 2003;278:34347–55.

    Article  CAS  PubMed  Google Scholar 

  63. Carroll RC, Lissin DV, von Zastrow M, Nicoll RA, Malenka RC. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nat Neurosci. 1999;2:454–60.

    Article  CAS  PubMed  Google Scholar 

  64. Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science. 1999;284:1811–6.

    Article  CAS  PubMed  Google Scholar 

  65. Casadio A, Martin KC, Giustetto M, Zhu H, Chen M, Bartsch D, et al. A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell. 1999;99:221–37.

    Article  CAS  PubMed  Google Scholar 

  66. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, et al. A brain-specific microRNA regulates dendritic spine development. Nature. 2006;439:283–9.

    Article  CAS  PubMed  Google Scholar 

  67. Schratt G. microRNAs at the synapse. Nat Rev Neurosci. 2009;10:842–9.

    Article  CAS  PubMed  Google Scholar 

  68. Chandrasekar V, Dreyer JL. microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity. Mol Cell Neurosci. 2009;42:350–62.

    Article  CAS  PubMed  Google Scholar 

  69. Cullen BR. Transcription and processing of human microRNA precursors. Mol Cell. 2004;16:861–5.

    Article  CAS  PubMed  Google Scholar 

  70. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18:3016–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23:185–8.

    Article  CAS  PubMed  Google Scholar 

  72. Dani VS, Nelson SB. Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome. J Neurosci. 2009;29:11263–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 2008;105:13556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by grants 81130087, 81671322 (to J-GL) and 81773710 (to Y-JW) from National Natural Science Foundation of China, by grant 2015CB553502 (to J-GL) from the Ministry of Sciences and Technology of China, by grant 2017334 (to Y-JW) from the Youth Innovation Promotion Association of the Chinese Academy of Sciences.

Funding

Funding acquisition, J-GL and Y-JW.

Author information

Author notes

  1. These authors contributed equally: Y-J Wang, C Yu, W-W Wu

Authors and Affiliations

  1. Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Yu-Jun Wang, Chuan Yu, Wei-Wei Wu, Yun-Yue Ju, Yao Liu, Jian-Dong Long, Gui-Ying Zan, Le-Sha Zhang, Jing-Rui Chai & Jing-Gen Liu

  2. Department of Neurobiology and Acupuncture Research, The Third Clinical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    Chi Xu, Zhong Chen & Jing-Gen Liu

  3. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Xiang-Yan Wei

Authors
  1. Yu-Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chuan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei-Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun-Yue Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chi Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian-Dong Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gui-Ying Zan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiang-Yan Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Le-Sha Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jing-Rui Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zhong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jing-Gen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J-GL, Y-JW, and ZC designed the experiment. Y-JW, CY, W-WW, YYJ, and YL performed the experiments with the assistance of J-DL, G-YZ, X-YW, L-SZ, J-RC Statistical data analysis was performed by Y-JW, CY, and W-WW. This manuscript was written by Y-JW and CX and was revised by J-GL and ZC.

Corresponding authors

Correspondence to Yu-Jun Wang, Zhong Chen or Jing-Gen Liu.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, YJ., Yu, C., Wu, WW. et al. Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory. Mol Psychiatry 26, 6218–6236 (2021). https://doi.org/10.1038/s41380-021-01111-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-021-01111-3

This article is cited by

Search

Advanced search

Quick links