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LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites

Abstract

The propagation and integration of signals in the dendrites of pyramidal neurons is regulated, in part, by the distribution and biophysical properties of voltage-gated ion channels. It is thus possible that any modification of these channels in a specific part of the dendritic tree might locally alter these signaling processes. Using dendritic and somatic whole-cell recordings, combined with calcium imaging in rat hippocampal slices, we found that the induction of long-term potentiation (LTP) was accompanied by a local increase in dendritic excitability that was dependent on the activation of NMDA receptors. These changes favored the back-propagation of action potentials into this dendritic region with a subsequent boost in the Ca2+ influx. Dendritic cell-attached patch recordings revealed a hyperpolarized shift in the inactivation curve of transient, A-type K+ currents that can account for the enhanced excitability. These results suggest an important mechanism associated with LTP for shaping signal processing and controlling dendritic function.

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Figure 1: Theta-burst pairing (TBP) induced strong and pathway-specific LTP.
Figure 2: Profile of b-AP-induced Ca2+ signals along the main apical dendrite.
Figure 3: Increase in dendritic Ca2+ signals from b-APs after LTP induction.
Figure 4: LTP was accompanied by an increase in dendritic b-AP amplitude.
Figure 5: Distal dendritic b-APs and Ca2+ signals—LTP.
Figure 6: Distal dendritic b-APs and Ca2+ signals—LTP block.
Figure 7: Dendrite-attached patch recordings revealed an increase in synaptic input with LTP.
Figure 8: Hyperpolarized shift in steady-state inactivation of distal dendritic IA with LTP.

References

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

    Article  CAS  Google Scholar 

  2. Johnston, D., Magee, J.C., Colbert, C.M. & Christie, B.R. Active properties of neuronal dendrites. Annu. Rev. Neurosci. 19, 165–186 (1996).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Jaffe, D.B. et al. The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons. Nature 357, 244–246 (1992).

    Article  CAS  Google Scholar 

  5. Miyakawa, H. et al. Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels. Neuron 9, 1163–1173 (1992).

    Article  CAS  Google Scholar 

  6. Spruston, N., Schiller, Y., Stuart, G. & Sakmann, B. Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268, 297–300 (1995).

    Article  CAS  Google Scholar 

  7. Frick, A., Magee, J., Koester, H.J., Migliore, M. & Johnston, D. Normalization of Ca2+ signals by small oblique dendrites of CA1 pyramidal neurons. J. Neurosci. 23, 3243–3250 (2003).

    Article  CAS  Google Scholar 

  8. Yuan, L.L., Adams, J.P., Swank, M., Sweatt, J.D. & Johnston, D. Protein kinase modulation of dendritic K+ channels in hippocampus involves a mitogen-activated protein kinase pathway. J. Neurosci. 22, 4860–4868 (2002).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Ramakers, G.M. & Storm, J.F. A postsynaptic transient K+ current modulated by arachidonic acid regulates synaptic integration and threshold for LTP induction in hippocampal pyramidal cells. Proc. Natl. Acad. Sci. USA 99, 10144–10149 (2002).

    Article  CAS  Google Scholar 

  11. Johnston, D. et al. Active dendrites, potassium channels and synaptic plasticity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 358, 667–674 (2003).

    Article  CAS  Google Scholar 

  12. Magee, J.C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997).

    Article  CAS  Google Scholar 

  13. Watanabe, S., Hoffman, D.A., Migliore, M. & Johnston, D. Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons. Proc. Natl. Acad. Sci. USA 99, 8366–8371 (2002).

    Article  CAS  Google Scholar 

  14. Johnston, D., Hoffman, D.A., Colbert, C.M. & Magee, J.C. Regulation of back-propagating action potentials in hippocampal neurons. Curr. Opin. Neurobiol. 9, 288–292 (1999).

    Article  CAS  Google Scholar 

  15. Muller, W. & Bittner, K. Differential oxidative modulation of voltage-dependent K+ currents in rat hippocampal neurons. J. Neurophysiol. 87, 2990–2995 (2002).

    Article  Google Scholar 

  16. Colbert, C.M. & Pan, E. Arachidonic acid reciprocally alters the availability of transient and sustained dendritic K+ channels in hippocampal CA1 pyramidal neurons. J. Neurosci. 19, 8163–8171 (1999).

    Article  CAS  Google Scholar 

  17. Tsubokawa, H. & Ross, W.N. Muscarinic modulation of spike backpropagation in the apical dendrites of hippocampal CA1 pyramidal neurons. J. Neurosci. 17, 5782–5791 (1997).

    Article  CAS  Google Scholar 

  18. Schrader, L.A., Anderson, A.E., Varga, A.W., Levy, M. & Sweatt, J.D. The other half of Hebb: K+ channels and the regulation of neuronal excitability in the hippocampus. Mol. Neurobiol. 25, 51–66 (2002).

    Article  CAS  Google Scholar 

  19. Bliss, T.V. & Collingridge, G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).

    Article  CAS  Google Scholar 

  20. Bliss, T.V. & Gardner-Medwin, A.R. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J. Physiol. 232, 357–374 (1973).

    Article  CAS  Google Scholar 

  21. Alkon, D.L., Lederhendler, I. & Shoukimas, J.J. Primary changes of membrane currents during retention of associative learning. Science 215, 693–695 (1982).

    Article  CAS  Google Scholar 

  22. Turrigiano, G., Abbott, L.F. & Marder, E. Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264, 974–977 (1994).

    Article  CAS  Google Scholar 

  23. Aizenman, C.D. & Linden, D.J. Rapid, synaptically driven increases in the intrinsic excitability of cerebellar deep nuclear neurons. Nat. Neurosci. 3, 109–111 (2000).

    Article  CAS  Google Scholar 

  24. Wang, Z., Xu, N.L., Wu, C.P., Duan, S. & Poo, M.M. Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications. Neuron 37, 463–472 (2003).

    Article  CAS  Google Scholar 

  25. Yasuda, R., Sabatini, B.L. & Svoboda, K. Plasticity of calcium channels in dendritic spines. Nat. Neurosci. 6, 948–955 (2003).

    Article  CAS  Google Scholar 

  26. Magee, J.C. Voltage-gated ion channels in dendrites. in Dendrites (eds. Stuart, G., Spruston, N. & Hausser, M.) 139–160 (Oxford Univ. Press, Oxford, UK, 1999).

    Google Scholar 

  27. Reyes, A. Influence of dendritic conductances on the input-output properties of neurons. Annu. Rev. Neurosci. 24, 653–675 (2001).

    Article  CAS  Google Scholar 

  28. Hoffman, D.A., Sprengel, R. & Sakmann, B. Molecular dissection of hippocampal theta-burst pairing potentiation. Proc. Natl. Acad. Sci. USA 99, 7740–7745 (2002).

    Article  CAS  Google Scholar 

  29. Christie, B.R., Eliot, L.S., Ito, K., Miyakawa, H. & Johnston, D. Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx. J. Neurophysiol. 73, 2553–2557 (1995).

    Article  CAS  Google Scholar 

  30. Golding, N.L., Staff, N.P. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002).

    Article  CAS  Google Scholar 

  31. Hodgkin, A.L. & Katz, B. The effect of sodium ions on the electrical activity of the giant axon of the squid. J. Physiol. (Lond.) 108, 37–77 (1949).

    Article  CAS  Google Scholar 

  32. Colbert, C.M., Magee, J.C., Hoffman, D.A. & Johnston, D. Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons. J. Neurosci. 17, 6512–6521 (1997).

    Article  CAS  Google Scholar 

  33. Magee, J.C. & Johnston, D. Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268, 301–304 (1995).

    Article  CAS  Google Scholar 

  34. Alonso, G. & Widmer, H. Clustering of KV4.2 potassium channels in postsynaptic membrane of rat supraoptic neurons: an ultrastructural study. Neuroscience 77, 617–621 (1997).

    Article  CAS  Google Scholar 

  35. Gasparini, S. & Magee, J.C. Phosphorylation-dependent differences in the activation properties of distal and proximal dendritic Na+ channels in rat CA1 hippocampal neurons. J. Physiol. 541, 665–672 (2002).

    Article  CAS  Google Scholar 

  36. Cantrell, A.R. & Catterall, W.A. Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat. Rev. Neurosci. 2, 397–407 (2001).

    Article  CAS  Google Scholar 

  37. Colbert, C.M. & Johnston, D. Protein kinase C activation decreases activity-dependent attenuation of dendritic Na+ current in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 79, 491–495 (1998).

    Article  CAS  Google Scholar 

  38. Magee, J.C. & Carruth, M. Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons. J. Neurophysiol. 82, 1895–1901 (1999).

    Article  CAS  Google Scholar 

  39. Tsubokawa, H., Offermanns, S., Simon, M. & Kano, M. Calcium-dependent persistent facilitation of spike backpropagation in the CA1 pyramidal neurons. J. Neurosci. 20, 4878–4884 (2000).

    Article  CAS  Google Scholar 

  40. Quirk, M.C., Blum, K.I. & Wilson, M.A. Experience-dependent changes in extracellular spike amplitude may reflect regulation of dendritic action potential back-propagation in rat hippocampal pyramidal cells. J. Neurosci. 21, 240–248 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  42. Linden, D.J. The return of the spike: postsynaptic action potentials and the induction of LTP and LTD. Neuron 22, 661–666 (1999).

    Article  CAS  Google Scholar 

  43. Poirazi, P. & Mel, B.W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).

    Article  CAS  Google Scholar 

  44. Poirazi, P., Brannon, T. & Mel, B.W. Pyramidal neuron as two-layer neural network. Neuron 37, 989–999 (2003).

    Article  CAS  Google Scholar 

  45. Abraham, W.C., Gustafsson, B. & Wigstrom, H. Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J. Physiol. 394, 367–380 (1987).

    Article  CAS  Google Scholar 

  46. Lu, Y.M., Mansuy, I.M., Kandel, E.R. & Roder, J. Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP. Neuron 26, 197–205 (2000).

    Article  CAS  Google Scholar 

  47. Staff, N.P. & Spruston, N. Intracellular correlate of EPSP-spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation. Hippocampus 13, 801–805 (2003).

    Article  CAS  Google Scholar 

  48. Taube, J.S. & Schwartzkroin, P.A. Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity. J. Neurosci. 8, 1632–1644 (1988).

    Article  CAS  Google Scholar 

  49. Chavez-Noriega, L.E., Halliwell, J.V. & Bliss, T.V. A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices. Exp. Brain Res. 79, 633–641 (1990).

    Article  CAS  Google Scholar 

  50. Jester, J.M., Campbell, L.W. & Sejnowski, T.J. Associative EPSP-spike potentiation induced by pairing orthodromic and antidromic stimulation in rat hippocampal slices. J. Physiol. 484, 689–705 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to acknowledge L. Schexnayder for early work on this project at Baylor and thank H. Miyakawa and M. Inoue for help with the project at the MBL. In addition, we thank X. Chen, R. Gray, M. Haque, M. Migliore, R. Chitwood, N. Poolos, A. Jeromin and M. Ginger for important contributions. Supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) (D.J.& J.M.), the Human Frontier Science Program (D.J.) and the Alexander von Humboldt Foundation (A.F.).

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Correspondence to Daniel Johnston.

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Frick, A., Magee, J. & Johnston, D. LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites. Nat Neurosci 7, 126–135 (2004). https://doi.org/10.1038/nn1178

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