Skip to main content

Thank you for visiting 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.

Synaptic amplification by dendritic spines enhances input cooperativity


Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons1,2 and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity3,4,5,6,7,8. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines9,10,11,12. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation3,4,5,6,7,8,13,14,15,16,17,18. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (Rneck) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that Rneck is large enough (500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by 1.5- to 45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an Rneck-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons19,20,21.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Measurement of voltage amplitude ratio across apical trunk spine necks.
Figure 2: Spine neck voltage amplitude ratio varies as a function of dendritic compartment.
Figure 3: Spine-to-branch voltage amplitude ratio is mediated by dendritic impedance.
Figure 4: Spines enhance the cooperative interaction among multiple inputs.


  1. Ramón y Cajal, S. Estructura de los centros nerviosos de las aves. Rev. Trim. Histol. Norm. Patol. 1, 1–10 (1888)

    Google Scholar 

  2. Bourne, J. N. & Harris, K. M. Balancing structure and function at hippocampal dendritic spines. Annu. Rev. Neurosci. 31, 47–67 (2008)

    CAS  Article  Google Scholar 

  3. Rall, W. Theory of physiological properties of dendrites. Ann. NY Acad. Sci. 96, 1071–1092 (1962)

    ADS  CAS  Article  Google Scholar 

  4. Rall, W. in Cellular Mechanisms Subserving Changes in Neuronal Activity (ed Woody, C. D. et al.) Brain Information Service Report No. 3 (Univ. of California, 1974)

    Google Scholar 

  5. Miller, J. P., Rall, W. & Rinzel, J. Synaptic amplification by active membrane in dendritic spines. Brain Res. 325, 325–330 (1985)

    CAS  Article  Google Scholar 

  6. Koch, C. & Zador, A. The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization. J. Neurosci. 13, 413–422 (1993)

    CAS  Article  Google Scholar 

  7. Yuste, R. Dendritic spines and distributed circuits. Neuron 71, 772–781 (2011)

    CAS  Article  Google Scholar 

  8. Hao, J. & Oertner, T. G. Depolarization gates spine calcium transients and spike-timing-dependent potentiation. Curr. Opin. Neurobiol. 22, 509–515 (2012)

    CAS  Article  Google Scholar 

  9. Guthrie, P. B., Segal, M. & Kater, S. B. Independent regulation of calcium revealed by imaging dendritic spines. Nature 354, 76–80 (1991)

    ADS  CAS  Article  Google Scholar 

  10. Yuste, R. & Denk, W. Dendritic spines as basic functional units of neuronal integration. Nature 375, 682–684 (1995)

    ADS  CAS  Article  Google Scholar 

  11. Yasuda, R. & Murakoshi, H. The mechanisms underlying the spatial spreading of signaling activity. Curr. Opin. Neurobiol. 21, 313–321 (2011)

    CAS  Article  Google Scholar 

  12. Chen, Y. & Sabatini, B. L. Signaling in dendritic spines and spine microdomains. Curr. Opin. Neurobiol. 22, 389–396 (2012)

    CAS  Article  Google Scholar 

  13. Svoboda, K., Tank, D. W. & Denk, W. Direct measurement of coupling between dendritic spines and shaft. Science 272, 716–719 (1996)

    ADS  CAS  Article  Google Scholar 

  14. Grunditz, A., Holbro, N., Tian, L., Zuo, Y. & Oertner, T. G. Spine neck plasticity controls postsynaptic calcium signals through electrical compartmentalization. J. Neurosci. 28, 13457–13466 (2008)

    CAS  Article  Google Scholar 

  15. Bloodgood, B. L. & Sabatini, B. L. Neuronal activity regulates diffusion across the neck of dendritic spines. Science 310, 866–869 (2005)

    ADS  CAS  Article  Google Scholar 

  16. Palmer, L. M. & Stuart, G. J. Membrane potential changes in dendritic spines during action potentials and synaptic input. J. Neurosci. 29, 6897–6903 (2009)

    CAS  Article  Google Scholar 

  17. Bloodgood, B. L., Giessel, A. J. & Sabatini, B. L. Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines. PLoS Biol. 7, e1000190 (2009)

    Article  Google Scholar 

  18. Tsay, D. & Yuste, R. On the electrical function of dendritic spines. Trends Neurosci. 27, 77–83 (2004)

    CAS  Article  Google Scholar 

  19. London, M. & Häusser, M. Dendritic computation. Annu. Rev. Neurosci. 28, 503–532 (2005)

    CAS  Article  Google Scholar 

  20. Wu, X. E. & Mel, B. W. Capacity-enhancing synaptic learning rules in a medial temporal lobe online learning model. Neuron 62, 31–41 (2009)

    CAS  Article  Google Scholar 

  21. Legenstein, R. & Maass, W. Branch-specific plasticity enables self-organization of nonlinear computation in single neurons. J. Neurosci. 31, 10787–10802 (2011)

    CAS  Article  Google Scholar 

  22. Magee, J. C. & Cook, E. P. Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons. Nature Neurosci. 3, 895–903 (2000)

    CAS  Article  Google Scholar 

  23. Bloodgood, B. L. & Sabatini, B. L. Nonlinear regulation of unitary synaptic signals by CaV2. 3 voltage-sensitive calcium channels located in dendritic spines. Neuron 53, 249–260 (2007)

    CAS  Article  Google Scholar 

  24. Jaffe, D. B. & Carnevale, N. T. Passive normalization of synaptic integration influenced by dendritic architecture. J. Neurophysiol. 82, 3268–3285 (1999)

    CAS  Article  Google Scholar 

  25. Gulledge, A. T., Carnevale, N. T. & Stuart, G. J. Electrical advantages of dendritic spines. PLoS ONE 7, e36007 (2012)

    ADS  CAS  Article  Google Scholar 

  26. Branco, T., Clark, B. A. & Häusser, M. Dendritic discrimination of temporal input sequences in cortical neurons. Science 329, 1671–1675 (2010)

    ADS  CAS  Article  Google Scholar 

  27. Losonczy, A., Makara, J. K. & Magee, J. C. Compartmentalized dendritic plasticity and input feature storage in neurons. Nature 452, 436–441 (2008)

    ADS  CAS  Article  Google Scholar 

  28. Makara, J. K., Losonczy, A., Wen, Q. & Magee, J. C. Experience-dependent compartmentalized dendritic plasticity in rat hippocampal CA1 pyramidal neurons. Nature Neurosci. 12, 1485–1487 (2009)

    CAS  Article  Google Scholar 

  29. Harvey, C. D. & Svoboda, K. Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature 450, 1195–1200 (2007)

    ADS  CAS  Article  Google Scholar 

  30. Gasparini, S. & Magee, J. C. State-dependent dendritic computation in hippocampal CA1 pyramidal neurons. J. Neurosci. 26, 2088–2100 (2006)

    CAS  Article  Google Scholar 

  31. Ji, N., Magee, J. C. & Betzig, E. High-speed, low-photodamage nonlinear imaging using passive pulse splitters. Nature Methods 5, 197–202 (2008)

    CAS  Article  Google Scholar 

  32. Johnston, D. & Wu, S. Foundations of Cellular Neurophysiology Ch. 13 400–411 (MIT Press, 1995)

    Google Scholar 

  33. Hines, M. L. & Carnevale, N. T. The neuron simulation environment. Neural Comput. 9, 1179–1209 (1997)

    CAS  Article  Google Scholar 

  34. Golding, N. L., Kath, W. L. & Spruston, N. Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites. J. Neurophysiol. 86, 2998–3010 (2001)

    CAS  Article  Google Scholar 

  35. Golding, N. L., Mickus, T. J., Katz, Y., Kath, W. L. & Spruston, N. Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites. J. Physiol. (Lond.) 568, 69–82 (2005)

    CAS  Article  Google Scholar 

  36. Magee, J. C. Dendritic lh normalizes temporal summation in hippocampal CA1 neurons. Nature Neurosci. 2, 508–514 (1999)

    CAS  Article  Google Scholar 

  37. Hoffman, D. A., Magee, J. C., Colbert, C. M. & Johnston, D. K. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387, 869–875 (1997)

    ADS  CAS  Article  Google Scholar 

  38. Katz, Y. et al. Synapse distribution suggests a two-stage model of dendritic integration in CA1 pyramidal neurons. Neuron 63, 171–177 (2009)

    CAS  Article  Google Scholar 

  39. Dowell, M. & Jarratt, P. A modified regula falsi method for computing the root of an equation. Bit Numerical Mathematics 11, 168–174 (1971)

    MathSciNet  Article  Google Scholar 

Download references


We thank A. Milstein, S. Gale and R. Chitwood for help in creating analysis tools and G. Murphy, S. Williams and D. Johnston for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (NS-046064, NS-077601) and the Wellcome Trust (International Senior Research Fellowship to J.K.M., grant number 090915).

Author information

Authors and Affiliations



M.T.H., J.K.M. and J.C.M. conceived the project and designed the experiments. M.T.H. and J.K.M. performed all experiments and data analysis. N.S., W.L.K. and J.C.M. performed computer simulations. M.T.H., J.K.M. and J.C.M. wrote the paper with comments from all authors.

Corresponding author

Correspondence to Jeffrey C. Magee.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-9 and Supplementary Text and Data, which includes a Supplementary Discussion. (PDF 6317 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Harnett, M., Makara, J., Spruston, N. et al. Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491, 599–602 (2012).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing