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Graves AR, Roth RH, Tan HL, et al. Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors. Elife. 2021;10doi: 10.7554/eLife.66809.
Graves, A. R., Roth, R. H., Tan, H. L., Zhu, Q., Bygrave, A. M., Lopez-Ortega, E., Hong, I., Spiegel, A. C., Johnson, R. C., Vogelstein, J. T., Tward, D. J., Miller, M. I., & Huganir, R. L. (2021). Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors. eLife, 10. https://doi.org/10.7554/eLife.66809
Graves, Austin R, et al. "Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors." eLife vol. 10 (2021). doi: https://doi.org/10.7554/eLife.66809
Graves AR, Roth RH, Tan HL, Zhu Q, Bygrave AM, Lopez-Ortega E, Hong I, Spiegel AC, Johnson RC, Vogelstein JT, Tward DJ, Miller MI, Huganir RL. Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors. Elife. 2021 Oct 18;10. doi: 10.7554/eLife.66809. PMID: 34658338; PMCID: PMC8616579.
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Elife. 2021 Oct 18;10. doi: 10.7554/eLife.66809.

Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors.

eLife

Austin R Graves, Richard H Roth, Han L Tan, Qianwen Zhu, Alexei M Bygrave, Elena Lopez-Ortega, Ingie Hong, Alina C Spiegel, Richard C Johnson, Joshua T Vogelstein, Daniel J Tward, Michael I Miller, Richard L Huganir

Affiliations

  1. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.
  2. Kavli Neuroscience Discovery Institute, Baltimore, United States.
  3. Center for Imaging Science, Johns Hopkins University School of Engineering, Baltimore, United States.
  4. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States.

PMID: 34658338 PMCID: PMC8616579 DOI: 10.7554/eLife.66809

Abstract

Elucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition and disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite of innovative methodologies that break through these barriers: a new knockin mouse line with fluorescently tagged endogenous AMPA receptors, two-photon imaging of hundreds of thousands of labeled synapses in behaving mice, and computer vision-based automatic synapse detection. Using these tools, we can longitudinally track how the strength of populations of synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synapses undergoing changes in strength following sensory experience. More generally, these tools can be used as an optical probe capable of measuring functional synapse strength across entire brain areas during any behavioral paradigm, describing complex system-wide changes with molecular precision.

© 2021, Graves et al.

Keywords: AMPA receptor; behavior; in vivo imaging; mouse; neuroscience; plasticity; synapse

Conflict of interest statement

AG, RR, HT, QZ, AB, EL, IH, AS, RJ, JV, DT, RH No competing interests declared, MM Dr. Miller is a joint owner of AnatomyWorks. Dr. Miller's relationship with Anatomy-Works is being handled under full

References

  1. Nature. 2014 Nov 6;515(7525):116-9 - PubMed
  2. Cold Spring Harb Perspect Biol. 2012 May 01;4(5): - PubMed
  3. Nature. 2012 Dec 13;492(7428):247-51 - PubMed
  4. Brain Res. 1978 Nov 24;157(2):277-93 - PubMed
  5. Nat Neurosci. 2009 Jul;12(7):897-904 - PubMed
  6. Nature. 1977 Apr 21;266(5604):736-7 - PubMed
  7. Science. 2017 Sep 8;357(6355):1033-1036 - PubMed
  8. eNeuro. 2021 May 21;8(3): - PubMed
  9. J Neurosci. 2016 Apr 13;36(15):4276-95 - PubMed
  10. Neuron. 2017 Jan 18;93(2):281-290 - PubMed
  11. Neuron. 2015 Jan 7;85(1):173-189 - PubMed
  12. Nat Methods. 2019 Dec;16(12):1233-1246 - PubMed
  13. PLoS Biol. 2006 Nov;4(11):e370 - PubMed
  14. Nature. 1997 Feb 6;385(6616):533-6 - PubMed
  15. Nature. 1998 Jul 9;394(6689):192-5 - PubMed
  16. Neuron. 2009 Nov 12;64(3):381-90 - PubMed
  17. Science. 2017 Feb 3;355(6324):511-515 - PubMed
  18. Nat Methods. 2019 Dec;16(12):1226-1232 - PubMed
  19. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):3948-3953 - PubMed
  20. Nat Commun. 2021 May 17;12(1):2881 - PubMed
  21. Nat Rev Neurosci. 2009 Sep;10(9):647-58 - PubMed
  22. Elife. 2020 Mar 03;9: - PubMed
  23. Sci Rep. 2020 Aug 19;10(1):14014 - PubMed
  24. Annu Rev Physiol. 2009;71:261-82 - PubMed
  25. Nature. 2017 Nov 8;551(7679):232-236 - PubMed
  26. Mol Cell Neurosci. 2006 Apr;31(4):702-12 - PubMed
  27. J Neurosci. 2013 Jul 31;33(31):12586-98 - PubMed
  28. Nat Neurosci. 2016 Dec;19(12):1553-1562 - PubMed
  29. Nat Methods. 2012 Jun 28;9(7):676-82 - PubMed
  30. Nat Neurosci. 2015 Mar;18(3):402-7 - PubMed
  31. J Neurosci. 2006 Jun 28;26(26):7046-55 - PubMed
  32. Eur J Neurosci. 2017 Apr;45(7):912-921 - PubMed
  33. Nature. 1998 Feb 26;391(6670):892-6 - PubMed
  34. Annu Rev Neurosci. 2002;25:103-26 - PubMed
  35. Nature. 2009 Dec 17;462(7275):915-9 - PubMed
  36. Annu Rev Neurosci. 2015 Jul 8;38:127-49 - PubMed
  37. Curr Opin Neurobiol. 2012 Jun;22(3):461-9 - PubMed
  38. Front Neurosci. 2020 Feb 11;14:52 - PubMed
  39. Nat Neurosci. 2018 Jan;21(1):50-62 - PubMed
  40. J Neurosci. 2014 Feb 5;34(6):2075-86 - PubMed
  41. Neural Plast. 2012;2012:704103 - PubMed
  42. Behav Neurosci. 2007 Jun;121(3):559-69 - PubMed
  43. Nat Rev Neurosci. 2016 Jun;17(6):337-50 - PubMed
  44. Neuron. 2013 Oct 30;80(3):704-17 - PubMed
  45. Elife. 2021 Mar 10;10: - PubMed
  46. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15951-6 - PubMed
  47. J Neurosci. 2009 Apr 29;29(17):5587-96 - PubMed
  48. Science. 1999 Jun 11;284(5421):1805-11 - PubMed
  49. Neuron. 2011 Apr 14;70(1):109-20 - PubMed
  50. Elife. 2016 Jun 14;5: - PubMed
  51. Curr Opin Neurobiol. 2017 Aug;45:51-58 - PubMed
  52. Nat Neurosci. 2010 Nov;13(11):1433-40 - PubMed
  53. Nat Neurosci. 2001 Nov;4(11):1086-92 - PubMed
  54. Neuropharmacology. 2021 Oct 1;197:108710 - PubMed
  55. J Neurosci. 2014 Dec 10;34(50):16698-712 - PubMed
  56. Nat Rev Neurosci. 2008 Mar;9(3):206-21 - PubMed
  57. J Physiol. 1973 Jul;232(2):331-56 - PubMed
  58. J Neurosci. 2006 Feb 15;26(7):2000-9 - PubMed
  59. Cereb Cortex. 2017 Aug 1;27(8):4244-4256 - PubMed
  60. Nature. 2002 Dec 19-26;420(6917):788-94 - PubMed
  61. PLoS One. 2014 Apr 22;9(4):e95967 - PubMed
  62. PLoS One. 2009;4(3):e4714 - PubMed
  63. Neuron. 2020 Mar 4;105(5):895-908.e5 - PubMed
  64. Annu Rev Neurosci. 2011;34:389-412 - PubMed
  65. J Neurosci. 1997 Oct 1;17(19):7351-8 - PubMed
  66. Neuron. 2007 Mar 1;53(5):719-34 - PubMed
  67. Nature. 2009 Dec 17;462(7275):920-4 - PubMed
  68. Nat Neurosci. 2016 Aug 26;19(9):1142-53 - PubMed
  69. Elife. 2017 Jul 27;6: - PubMed
  70. J Neurosci. 2020 Feb 19;40(8):1596-1605 - PubMed
  71. Nat Methods. 2019 Jan;16(1):67-70 - PubMed
  72. Neuron. 2018 Aug 22;99(4):781-799.e10 - PubMed
  73. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7136-7141 - PubMed
  74. Neuron. 1998 Nov;21(5):1067-78 - PubMed
  75. Hum Mutat. 2013 Feb;34(2):385-94 - PubMed
  76. Science. 2018 Jun 22;360(6395):1349-1354 - PubMed
  77. Transl Psychiatry. 2019 Apr 18;9(1):142 - PubMed
  78. J Neurosci. 2004 Jun 2;24(22):5172-6 - PubMed
  79. Nat Neurosci. 2007 May;10(5):546-8 - PubMed
  80. Elife. 2019 Aug 14;8: - PubMed
  81. Behav Neurosci. 2004 Jun;118(3):643-7 - PubMed

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