In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons

Abstract

Dendritic Ca2+ action potentials in neocortical pyramidal neurons have been characterized in brain slices, but their presence and role in the intact neocortex remain unclear. Here we used two-photon microscopy to demonstrate Ca2+ electrogenesis in apical dendrites of deep-layer pyramidal neurons of rat barrel cortex in vivo. During whisker stimulation, complex spikes recorded intracellularly from distal dendrites and sharp waves in the electrocorticogram were accompanied by large dendritic [Ca2+] transients; these also occurred during bursts of action potentials recorded from somata of identified layer 5 neurons. The amplitude of the [Ca2+] transients was largest proximal to the main bifurcation, where sodium action potentials produced little Ca2+ influx. In some cases, synaptic stimulation evoked [Ca2+] transients without a concomitant action potential burst, suggesting variable coupling between dendrite and soma.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Dendritic recordings from deep neocortical pyramidal neurons.
Figure 2: Relationship between dendritic complex spikes, [Ca2+] transients and ECoG spikes.
Figure 3: Simultaneous somatic recording and distal dendritic imaging from intrinsically bursting layer 5 neurons.
Figure 4: Sensory-evoked dendritic [Ca2+] transients in layer 5 neurons.
Figure 5: [Ca2+] transients in the apical dendrite and somatic bursts of APs can occur in isolation.
Figure 6: Spatial profile of distal dendritic [Ca2+] transients.

References

  1. 1

    Yuste, R. & Tank, D. W. Dendritic integration in mammalian neurons, a century after Cajal. Neuron 16, 701–716 (1996).

    CAS  Article  Google Scholar 

  2. 2

    Stuart, G., Spruston, N., Sakmann, B. & Häusser, M. Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci. 20, 125– 131 (1997).

    CAS  Article  Google Scholar 

  3. 3

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

    CAS  Article  Google Scholar 

  4. 4

    Markram, H., Lübke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997).

    CAS  Article  Google Scholar 

  5. 5

    Schiller, J., Schiller, Y., Stuart, G. & Sakmann, B. Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons. J. Physiol. (Lond.) 505, 605– 616 (1997).

    CAS  Article  Google Scholar 

  6. 6

    Stuart, G., Schiller, J. & Sakmann, B. Action potential initiation and propagation in rat neocortical pyramidal neurons. J. Physiol. (Lond.) 505, 617–632 (1997).

    CAS  Article  Google Scholar 

  7. 7

    Cauller, L. J. & Connors, B. W. Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex. J. Neurosci. 14, 751–762 ( 1994).

    CAS  Article  Google Scholar 

  8. 8

    Bernander, O., Koch, C. & Douglas, R. J. Amplification and linearization of distal synaptic input to cortical pyramidal cells. J. Neurophysiol. 72, 2743–2753 (1994).

    CAS  Article  Google Scholar 

  9. 9

    Wong, R. K. & Prince, D. A. Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res. 159, 385–390 ( 1978).

    CAS  Article  Google Scholar 

  10. 10

    Rhodes, P. A. & Gray, C. M. Simulations of intrinsically bursting neocortical pyramidal neurons. Neural Comput. 6, 1086–1110 (1994).

    Article  Google Scholar 

  11. 11

    Larkum, M. E., Zhu, J. J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999).

    CAS  Article  Google Scholar 

  12. 12

    Connors, B. W. & Gutnick, M. J. Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci. 13, 99–104 (1990).

    CAS  Article  Google Scholar 

  13. 13

    Mason, A. & Larkman, A. Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. II. Electrophysiology. J. Neurosci. 10, 1415–1428 (1990).

    CAS  Article  Google Scholar 

  14. 14

    Lisman, J.E. Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci. 20, 38– 43 (1997).

    CAS  Article  Google Scholar 

  15. 15

    Silva, L. R., Amitai, Y. & Connors, B. W. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. Science 251, 432–435 (1991).

    CAS  Article  Google Scholar 

  16. 16

    Connors, B.W., Gutnick, M.J. & Prince, D.A. Electrophysiological properties of neocortical neurons in vitro. J. Neurophysiol. 48, 1302– 1320 (1982).

    CAS  Article  Google Scholar 

  17. 17

    Stafstrom, C. E., Schwindt, P. C., Chubb, M. C. & Crill, W. E. Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro. J. Neurophysiol. 53, 153–170 ( 1985).

    CAS  Article  Google Scholar 

  18. 18

    Reuveni, I., Friedman, A., Amitai, Y. & Gutnick, M. J. Stepwise repolarization from Ca2+ plateaus in neocortical pyramidal cells: evidence for nonhomogeneous distribution of HVA Ca2+ channels in dendrites. J. Neurosci. 13, 4609– 4621 (1993).

    CAS  Article  Google Scholar 

  19. 19

    Yuste, R., Gutnick, M. J., Saar, D., Delaney, K. R. & Tank, D. W. Ca2+ accumulations in dendrites of neocortical pyramidal neurons: an apical band and evidence for two functional compartments. Neuron 13, 23– 43 (1994).

    CAS  Article  Google Scholar 

  20. 20

    Amitai, Y., Friedman, A., Connors, B. W. & Gutnick, M. J. Regenerative activity in apical dendrites of pyramidal cells in neocortex. Cereb. Cortex 3, 26–38 (1993).

    CAS  Article  Google Scholar 

  21. 21

    Kim, H. G. & Connors, B. W. Apical dendrites of the neocortex: correlation between sodium- and calcium-dependent spiking and pyramidal cell morphology. J. Neurosci. 13, 5301– 5311 (1993).

    CAS  Article  Google Scholar 

  22. 22

    Seamans, J. K., Gorelova, N. A. & Yang, C. R. Contributions of voltage-gated Ca2+ channels in the proximal versus distal dendrites to synaptic integration in prefrontal cortical neurons. J. Neurosci. 17, 5936–5948 (1997).

    CAS  Article  Google Scholar 

  23. 23

    Schwindt, P. C. & Crill, W. E. Local and propagated dendritic action potentials evoked by glutamate iontophoresis on rat neocortical pyramidal neurons. J. Neurophysiol. 77, 2466–2483 (1997).

    CAS  Article  Google Scholar 

  24. 24

    Paré, D., Shink, E., Gaudreau, H., Destexhe, A. & Lang, E. J. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79, 1450–1460 ( 1998).

    Article  Google Scholar 

  25. 25

    Kim, H. G., Beierlein, M. & Connors, B. W. Inhibitory control of excitable dendrites in neocortex. J. Neurophysiol. 74, 1810– 1814 (1995).

    CAS  Article  Google Scholar 

  26. 26

    Paré, D., Lang, E. J. & Destexhe, A. Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: an intracellular and computational study. Neuroscience 84, 377–402 (1998).

    Article  Google Scholar 

  27. 27

    McCormick, D. A., Wang, Z. & Huguenard, J. Neurotransmitter control of neocortical neuronal activity and excitability. Cereb. Cortex 3, 387– 398 (1993).

    CAS  Article  Google Scholar 

  28. 28

    Pockberger, H. Electrophysiological and morphological properties of rat motor cortex neurons in vivo. Brain Res. 539, 181– 190 (1991).

    CAS  Article  Google Scholar 

  29. 29

    Zhu, J. J. & Connors, B. W. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. J. Neurophysiol. 81, 1171–1183 (1999).

    CAS  Article  Google Scholar 

  30. 30

    Nuñez, A., Amzica, F. & Steriade, M. Electrophysiology of cat association cortical cells in vivo: intrinsic properties and synaptic responses. J. Neurophysiol. 70, 418–430 ( 1993).

    Article  Google Scholar 

  31. 31

    Hirsch, J. A., Alonso, J. M. & Reid, R. C. Visually evoked calcium action potentials in cat striate cortex. Nature 378, 612– 616 (1995).

    CAS  Article  Google Scholar 

  32. 32

    Paré, D. & Lang, E. J. Calcium electrogenesis in neocortical pyramidal neurons in vivo. Eur. J. Neurosci. 10, 3164–3170 (1998).

    Article  Google Scholar 

  33. 33

    Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D. W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).

    CAS  Article  Google Scholar 

  34. 34

    Svoboda, K., Helmchen, F., Denk, W. & Tank, D. W. Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo. Nat. Neurosci. 2, 65–73 (1999).

    CAS  Article  Google Scholar 

  35. 35

    Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    CAS  Article  Google Scholar 

  36. 36

    Denk, W. & Svoboda, K. Photon upmanship: why multiphoton imaging is more than a gimmick. Neuron 18, 351–357 (1997).

    CAS  Article  Google Scholar 

  37. 37

    Kleinfeld, D., Mitra, P. P., Helmchen, F. & Denk, W. Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc. Natl. Acad. Sci. USA 95, 15741–15746 ( 1998).

    CAS  Article  Google Scholar 

  38. 38

    Arieli, A., Sterkin, A., Grinvald, A. & Aertsen, A. Dynamics of ongoing activity: explanation of the large variablility in evoked cortical responses. Science 273, 1868– 1871 (1996).

    CAS  Article  Google Scholar 

  39. 39

    Kandel, A. & Buzsáki, G. Cellular-synaptic generation of sleep spindles, spike-and-wave discharges, and thalamocortical responses in the neocortex of rat. J. Neurosci. 17, 6783–6797 (1997).

    CAS  Article  Google Scholar 

  40. 40

    Chagnac-Amitai, Y., Luhmann, H. J. & Prince, D. A. Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features. J. Comp. Neurol. 296, 598–613 (1990).

    CAS  Article  Google Scholar 

  41. 41

    Tseng, G. F. & Prince, D. A. Heterogeneity of rat corticospinal neurons. J. Comp. Neurol. 335, 92– 108 (1993).

    CAS  Article  Google Scholar 

  42. 42

    Baranyi, A., Szente, M. B. & Woody, C. D. Electrophysiological characterization of different types of neurons recorded in vivo in the motor cortex of the cat. I. Patterns of firing activity and synaptic responses. J. Neurophysiol. 69, 1850–1864 (1993).

    CAS  Article  Google Scholar 

  43. 43

    Buzsáki, G. & Kandel, A. Somadendritic backpropagation of action potentials in cortical pyramidal cells of the awake rat. J. Neurophysiol. 79, 1587–1591 (1998).

    Article  Google Scholar 

  44. 44

    Pinsky, P. F. & Rinzel, J. Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. J. Comput. Neurosci. 1, 39–60 (1994 ).

    CAS  Article  Google Scholar 

  45. 45

    Mainen, Z. F. & Sejnowski, T. J. Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 382, 363–366 (1996).

    CAS  Article  Google Scholar 

  46. 46

    Franceschetti, S. et al. Ionic mechanisms underlying burst firing in pyramidal neurons: intracellular study in rat sensorimotor cortex. Brain Res. 696, 127–139 (1995).

    CAS  Article  Google Scholar 

  47. 47

    Friedman, A. & Gutnick, M. J. Intracellular calcium and control of burst generation in neurons of guinea-pig neocortex in vitro. Eur. J. Neurosci. 1, 374–381 (1989).

    Article  Google Scholar 

  48. 48

    Wang, Z. & McCormick, D.A. Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R- ACPD. J. Neurosci. 13, 2199– 2216 (1993).

    CAS  Article  Google Scholar 

  49. 49

    Markram, H., Wang, Y. & Tsodyks, M. Differential signaling via the same axon of neocortical pyramidal neurons. Proc. Natl. Acad. Sci. USA 95, 5323–5328 (1998).

    CAS  Article  Google Scholar 

  50. 50

    Helmchen, F., Imoto, K. & Sakmann, B. Ca2+ buffering and action potential-evoked Ca2+ signaling in dendrites of pyramidal neurons. Biophys. J. 70, 1069–1081 (1996).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank G. Major and S. S.-H. Wang for comments on the manuscript and B. Burbach for help with histology. This work was supported by Lucent Technologies and the Whitehall Foundation, grants to K.S. from the NIH, the Pew and the Klingenstein Foundations and fellowships to F.H. from the Max-Planck Society and the Human Frontier Science Program.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Fritjof Helmchen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Helmchen, F., Svoboda, K., Denk, W. et al. In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nat Neurosci 2, 989–996 (1999). https://doi.org/10.1038/14788

Download citation

Further reading

Search

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