Measurement of Silent Synapses

  • Nicholas GrazianeEmail author
  • Yan Dong
Part of the Neuromethods book series (NM, volume 112)


In this chapter we describe the approaches that can be implemented to estimate the level of excitatory silent synapses. For each approach there are technical considerations, which we describe at the end of the chapter. However, before laying out the experimental design, a brief description of silent synapses as well as their functional role in physiology will precede.

Key words

Coefficient of variation Minimal stimulation 


  1. 1.
    Durand GM, Kovalchuk Y, Konnerth A (1996) Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381(6577):71–75CrossRefPubMedGoogle Scholar
  2. 2.
    Groc L, Gustafsson B, Hanse E (2006) AMPA signalling in nascent glutamatergic synapses: there and not there! Trends Neurosci 29(3):132–139CrossRefPubMedGoogle Scholar
  3. 3.
    Petralia RS, Esteban JA, Wang YX, Partridge JG, Zhao HM, Wenthold RJ, Malinow R (1999) Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat Neurosci 2(1):31–36CrossRefPubMedGoogle Scholar
  4. 4.
    Dong Y, Nestler EJ (2014) The neural rejuvenation hypothesis of cocaine addiction. Trends Pharmacol Sci 35(8):374–383CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hanse E, Seth H, Riebe I (2013) AMPA-silent synapses in brain development and pathology. Nat Rev Neurosci 14(12):839–850CrossRefPubMedGoogle Scholar
  6. 6.
    Hill TC, Zito K (2013) LTP-induced long-term stabilization of individual nascent dendritic spines. J Neurosci 33(2):678–686CrossRefPubMedGoogle Scholar
  7. 7.
    Isaac JT, Nicoll RA, Malenka RC (1995) Evidence for silent synapses: implications for the expression of LTP. Neuron 15(2):427–434CrossRefPubMedGoogle Scholar
  8. 8.
    Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274(5290):1133–1138CrossRefPubMedGoogle Scholar
  9. 9.
    Kerchner GA, Nicoll RA (2008) Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat Rev Neurosci 9(11):813–825CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Liao D, Hessler NA, Malinow R (1995) Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375(6530):400–404CrossRefPubMedGoogle Scholar
  11. 11.
    Marie H, Morishita W, Yu X, Calakos N, Malenka RC (2005) Generation of silent synapses by acute in vivo expression of CaMKIV and CREB. Neuron 45(5):741–752CrossRefPubMedGoogle Scholar
  12. 12.
    Montgomery JM, Pavlidis P, Madison DV (2001) Pair recordings reveal all-silent synaptic connections and the postsynaptic expression of long-term potentiation. Neuron 29(3):691–701CrossRefPubMedGoogle Scholar
  13. 13.
    Rumpel S, Hatt H, Gottmann K (1998) Silent synapses in the developing rat visual cortex: evidence for postsynaptic expression of synaptic plasticity. J Neurosci 18(21):8863–8874PubMedGoogle Scholar
  14. 14.
    Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, Malinow R (2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52(5):831–843CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ting JT, Kelley BG, Lambert TJ, Cook DG, Sullivan JM (2007) Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc Natl Acad Sci U S A 104(1):353–358CrossRefPubMedGoogle Scholar
  16. 16.
    Huang YH, Lin Y, Mu P, Lee BR, Brown TE, Wayman G, Marie H, Liu W, Yan Z, Sorg BA, Schluter OM, Zukin RS, Dong Y (2009) In vivo cocaine experience generates silent synapses. Neuron 63(1):40–47CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lee BR, Ma YY, Huang YH, Wang X, Otaka M, Ishikawa M, Neumann PA, Graziane NM, Brown TE, Suska A, Guo C, Lobo MK, Sesack SR, Wolf ME, Nestler EJ, Shaham Y, Schluter OM, Dong Y (2013) Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving. Nat Neurosci 16(11):1644–1651CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pascoli V, Turiault M, Luscher C (2012) Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour. Nature 481(7379):71–75CrossRefGoogle Scholar
  19. 19.
    Robinson TE, Kolb B (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11(5):1598–1604CrossRefPubMedGoogle Scholar
  20. 20.
    Kessels HW, Nabavi S, Malinow R (2013) Metabotropic NMDA receptor function is required for beta-amyloid-induced synaptic depression. Proc Natl Acad Sci U S A 110(10):4033–4038CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 8(8):1051–1058CrossRefPubMedGoogle Scholar
  22. 22.
    Faber DS, Korn H (1991) Applicability of the coefficient of variation method for analyzing synaptic plasticity. Biophys J 60(5):1288–1294CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kullmann DM (1994) Amplitude fluctuations of dual-component EPSCs in hippocampal pyramidal cells: implications for long-term potentiation. Neuron 12(5):1111–1120CrossRefPubMedGoogle Scholar
  24. 24.
    Manabe T, Wyllie DJ, Perkel DJ, Nicoll RA (1993) Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus. J Neurophysiol 70(4):1451–1459PubMedGoogle Scholar
  25. 25.
    Koya E, Cruz FC, Ator R, Golden SA, Hoffman AF, Lupica CR, Hope BT (2012) Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization. Nat Neurosci 15(11):1556–1562CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ahmadian G, Ju W, Liu L, Wyszynski M, Lee SH, Dunah AW, Taghibiglou C, Wang Y, Lu J, Wong TP, Sheng M, Wang YT (2004) Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD. EMBO J 23(5):1040–1050CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Wang Y, Ju W, Liu L, Fam S, D’Souza S, Taghibiglou C, Salter M, Wang YT (2004) alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor (AMPAR) endocytosis is essential for N-methyl-D-aspartate-induced neuronal apoptosis. J Biol Chem 279(40):41267–41270CrossRefPubMedGoogle Scholar
  28. 28.
    Wang YT (2008) Probing the role of AMPAR endocytosis and long-term depression in behavioural sensitization: relevance to treatment of brain disorders, including drug addiction. Br J Pharmacol 153(Suppl 1):S389–S395PubMedGoogle Scholar
  29. 29.
    Wong TP, Howland JG, Robillard JM, Ge Y, Yu W, Titterness AK, Brebner K, Liu L, Weinberg J, Christie BR, Phillips AG, Wang YT (2007) Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment. Proc Natl Acad Sci U S A 104(27):11471–11476CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Neuroscience DepartmentUniversity of PittsburghPittsburghUSA

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