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Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes


Dendritic spines are the primary site of excitatory synaptic input onto neurons, and are biochemically isolated from the parent dendritic shaft by their thin neck. However, due to the lack of direct electrical recordings from spines, the influence that the neck resistance has on synaptic transmission, and the extent to which spines compartmentalize voltage, specifically excitatory postsynaptic potentials, albeit critical, remains controversial. Here, we use quantum-dot-coated nanopipette electrodes (tip diameters 15–30 nm) to establish the first intracellular recordings from targeted spine heads under two-photon visualization. Using simultaneous somato-spine electrical recordings, we find that back propagating action potentials fully invade spines, that excitatory postsynaptic potentials are large in the spine head (mean 26 mV) but are strongly attenuated at the soma (0.5–1 mV) and that the estimated neck resistance (mean 420 MΩ) is large enough to generate significant voltage compartmentalization. Nanopipettes can thus be used to electrically probe biological nanostructures.

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Figure 1: Experimental overview.
Figure 2: The nanopipette membrane interface.
Figure 3: Nanopipette recordings from cultures.
Figure 4: Nanopipette recordings from neocortical slices.
Figure 5: Nanopipette recordings in spines reveals electrical compartmentalization.


  1. 1

    Yuste, R. Electrical compartmentalization in dendritic spines. Annu. Rev. Neurosci. 36, 429–449 (2013).

    CAS  Article  Google Scholar 

  2. 2

    Grunditz, Å., 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 

  3. 3

    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 

  4. 4

    Grutzendler, J., Kasthuri, N. & Gan, W.-B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).

    CAS  Article  Google Scholar 

  5. 5

    Yang, G., Pan, F. & Gan, W.-B. Stably maintained dendritic spines are associated with lifelong memories. Nature 462, 920–924 (2009).

    CAS  Article  Google Scholar 

  6. 6

    Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001).

    CAS  Article  Google Scholar 

  7. 7

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

    CAS  Article  Google Scholar 

  8. 8

    Müller, W. & Connor, J. A. Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses. Nature 354, 73–76 (1991).

    Article  Google Scholar 

  9. 9

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

    CAS  Article  Google Scholar 

  10. 10

    Harnett, M. T., Makara, J. K., Spruston, N., Kath, W. L. & Magee, J. C. Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491, 599–602 (2012).

    CAS  Article  Google Scholar 

  11. 11

    Perkel, D. H. & Perkel, D. J. Dendritic spines: role of active membrane in modulating synaptic efficacy. Brain Res. 325, 331–335 (1985).

    CAS  Article  Google Scholar 

  12. 12

    Shepherd, G. et al. Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. Proc. Natl Acad. Sci. USA 82, 2192–2195 (1985).

    CAS  Article  Google Scholar 

  13. 13

    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 

  14. 14

    Bloodgood, B. L., Giessel, A. J. & Sabatini, B. L. Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines. PLoS Biol. 7, 1–10 (2009).

    Article  Google Scholar 

  15. 15

    Araya, R., Jiang, J., Eisenthal, K. B. & Yuste, R. The spine neck filters membrane potentials. Proc. Natl Acad. Sci. USA 103, 17961–17966 (2006).

    CAS  Article  Google Scholar 

  16. 16

    Acker, C. D., Yan, P. & Loew, L. M. Single-voxel recording of voltage transients in dendritic spines. Biophys. J. 101, L11–L13 (2011).

    CAS  Article  Google Scholar 

  17. 17

    Segev, I. & Rall, W. Computational study of an excitable dendritic spine. J. Neurophysiol. 60, 499–523 (1988).

    CAS  Article  Google Scholar 

  18. 18

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

    CAS  Article  Google Scholar 

  19. 19

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

    CAS  Article  Google Scholar 

  20. 20

    Tønnesen, J., Katona, G., Rózsa, B. & Nägerl, U. V. Spine neck plasticity regulates compartmentalization of synapses. Nat. Neurosci. 17, 678–685 (2014).

    Article  Google Scholar 

  21. 21

    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 

  22. 22

    Hochbaum, D. R. et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat. Methods 11, 825–833 (2014).

    CAS  Article  Google Scholar 

  23. 23

    Acker, C. D., Hoyos, E. & Loew, L. M. EPSPs measured in proximal dendritic spines of cortical pyramidal neurons. eneuro 3, 1–13 (2016).

    Article  Google Scholar 

  24. 24

    Popovic, M. A., Gao, X., Carnevale, N. T. & Zecevic, D. Cortical dendritic spine heads are not electrically isolated by the spine neck from membrane potential signals in parent dendrites. Cerebral Cortex 24, 385–395 (2012).

    Article  Google Scholar 

  25. 25

    Popovic, M. A., Carnevale, N., Rozsa, B. & Zecevic, D. Electrical behaviour of dendritic spines as revealed by voltage imaging. Nat. Commun. 6, 8436 (2015).

    CAS  Article  Google Scholar 

  26. 26

    Nuriya, M., Jiang, J., Nemet, B., Eisenthal, K. B. & Yuste, R. Imaging membrane potential in dendritic spines. Proc. Natl Acad. Sci. USA 103, 786–790 (2006).

    CAS  Article  Google Scholar 

  27. 27

    Qing, Q. et al. Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions. Nat. Nanotech. 9, 142–147 (2014).

    CAS  Article  Google Scholar 

  28. 28

    Qing, Q. et al. Nanowire transistor arrays for mapping neural circuits in acute brain slices. Proc. Natl Acad. Sci. USA 107, 1882–1887 (2010).

    CAS  Article  Google Scholar 

  29. 29

    Robinson, J. T. et al. Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. Nat. Nanotech. 7, 180–184 (2012).

    CAS  Article  Google Scholar 

  30. 30

    Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010).

    CAS  Article  Google Scholar 

  31. 31

    Xie, C., Lin, Z., Hanson, L., Cui, Y. & Cui, B. Intracellular recording of action potentials by nanopillar electroporation. Nat. Nanotech. 7, 185–190 (2012).

    CAS  Article  Google Scholar 

  32. 32

    Singhal, R. et al. Multifunctional carbon-nanotube cellular endoscopes. Nat. Nanotech. 6, 57–64 (2011).

    CAS  Article  Google Scholar 

  33. 33

    Novak, P. et al. Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron 79, 1067–1077 (2013).

    CAS  Article  Google Scholar 

  34. 34

    Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotech. 8, 83–94 (2013).

    CAS  Article  Google Scholar 

  35. 35

    Fendyur, A. & Spira, M. E. Toward on-chip, in-cell recordings from cultured cardiomyocytes by arrays of gold mushroom-shaped microelectrodes. Front. Neuroeng. 5, 1–10 (2012).

    Article  Google Scholar 

  36. 36

    Hai, A., Shappir, J. & Spira, M. E. In-cell recordings by extracellular microelectrodes. Nat. Methods 7, 200–202 (2010).

    CAS  Article  Google Scholar 

  37. 37

    Angle, M. R. & Schaefer, A. T. Neuronal recordings with solid-conductor intracellular nanoelectrodes (SCINEs). PLoS ONE 7, e43194 (2012).

    CAS  Article  Google Scholar 

  38. 38

    Alivisatos, A. P. et al. Nanotools for neuroscience and brain activity mapping. ACS Nano 7, 1850–1866 (2013).

    CAS  Article  Google Scholar 

  39. 39

    Hu, H. & Jonas, P. A supercritical density of Na+ channels ensures fast signaling in GABAergic interneuron axons. Nat. Neurosci. 17, 686–693 (2014).

    CAS  Article  Google Scholar 

  40. 40

    Stuart, G. J. & Sakmann, B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367, 69–72 (1994).

    CAS  Article  Google Scholar 

  41. 41

    Stuart, G. J. & Häusser, M. Dendritic coincidence detection of EPSPs and action potentials. Nat. Neurosci. 4, 63–71 (2001).

    CAS  Article  Google Scholar 

  42. 42

    Holthoff, K., Zecevic, D. & Konnerth, A. Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons. J. Physiol. 588, 1085–1096 (2010).

    CAS  Article  Google Scholar 

  43. 43

    Andrasfalvy, B. K. et al. Quantum dot-based multiphoton fluorescent pipettes for targeted neuronal electrophysiology. Nat. Methods 11, 1237–1241 (2014).

    CAS  Article  Google Scholar 

  44. 44

    Purves, R. Microelectrode Methods for Intracellular Recording and Ionophoresis (Academic, 1981).

    Google Scholar 

  45. 45

    Ince, C. et al. Intracellular microelectrode measurements in small cells evaluated with the patch clamp technique. Biophys. J. 50, 1203–1209 (1986).

    CAS  Article  Google Scholar 

  46. 46

    Brette, R. et al. High-resolution intracellular recordings using a real-time computational model of the electrode. Neuron 59, 379–391 (2008).

    CAS  Article  Google Scholar 

  47. 47

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

    CAS  Article  Google Scholar 

  48. 48

    Lin, Z. C., Xie, C., Osakada, Y., Cui, Y. & Cui, B. Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nat. Commun. 5, 3206 (2014).

    Article  Google Scholar 

  49. 49

    Bi, G.-q. & Poo, M.-m. Distributed synaptic modification in neural networks induced by patterned stimulation. Nature 401, 792–796 (1999).

    CAS  Article  Google Scholar 

  50. 50

    Duan, X. et al. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat. Nanotech. 7, 174–179 (2012).

    CAS  Article  Google Scholar 

  51. 51

    Fu, T.-M. et al. Sub-10-nm intracellular bioelectronic probes from nanowire–nanotube heterostructures. Proc. Natl Acad. Sci. USA 111, 1259–1264 (2014).

    CAS  Article  Google Scholar 

  52. 52

    Almquist, B. D. & Melosh, N. A. Fusion of biomimetic stealth probes into lipid bilayer cores. Proc. Natl Acad. Sci. USA 107, 5815–5820 (2010).

    CAS  Article  Google Scholar 

  53. 53

    Angle, M. R., Cui, B. & Melosh, N. A. Nanotechnology and neurophysiology. Curr. Opin. Neurobiol. 32, 132–140 (2015).

    CAS  Article  Google Scholar 

  54. 54

    Beaudoin III, G. M. et al. Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat. Protoc. 7, 1741–1754 (2012).

    Article  Google Scholar 

  55. 55

    Packer, A. M. Understanding the Nervous System as an Information Processing Machine: Dense, Nonspecific, Canonical Microcircuit Architecture of Inhibition in Neocortex and a Neural Circuit for Angular Velocity Computation PhD thesis, Columbia Univ. (2011).

    Google Scholar 

  56. 56

    Garaj, S. et al. Graphene as a subnanometre trans-electrode membrane. Nature 467, 190–193 (2010).

    CAS  Article  Google Scholar 

  57. 57

    Araya, R. Input transformation by dendritic spines of pyramidal neurons. Front. Neuroanatomy, 8, 1–18 (2014).

    Article  Google Scholar 

  58. 58

    Denk, W., Yuste, R., Svoboda, K. & Tank, D. W. Imaging calcium dynamics in dendritic spines. Curr. Opin. Neurobiol. 6, 372–378 (1996).

    CAS  Article  Google Scholar 

  59. 59

    Thevenaz, P., Ruttimann, U. E. & Unser, M. A pyramid approach to subpixel registration based on intensity. IEEE Trans. Image Processing 7, 27–41 (1998).

    CAS  Article  Google Scholar 

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K.J. would like to thank M. Barbic of the applied physics and instrumentation group at Janelia Farms for initial assistance with initial SEM imaging. This work was supported by the National Institute of Mental Health (NIMH) (R01MH101218, R01MH100561) and the Kavli Institute of Brain Science. This material is also based on work supported by, or in part by, the US Army Research Laboratory and the US Army Research Office under contract number W911NF-12-1-0594 (MURI).

Author information




K.J. and R.Y. designed and conceptualized the study. J.J.H. performed slice preparation and provided technical support. I.J.-L.P., W.D.A.M.D.B. and J.S.O. synthesized, characterized and provided quantum dots. D.M.T. and K.J. performed SEM imaging. A.S. prepared cell cultures. D.S.P. provided technical support. O.S, K.L.S. and R.Y. advised on experiments. R.Y. supervised the overall study. K.J. performed all the experiments, modelling and analysis and wrote the manuscript. All the authors discussed the manuscript and provided comments.

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Correspondence to Krishna Jayant.

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The authors declare no competing financial interests.

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Jayant, K., Hirtz, J., Plante, IL. et al. Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes. Nature Nanotech 12, 335–342 (2017).

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