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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Yuste, R. & Tank, D.W. Dendritic integration in mammalian neurons, a century after Cajal. Neuron 16, 701–716 (1996).
Johnston, D., Magee, J.C., Colbert, C.M. & Christie, B.R. Active properties of neuronal dendrites. Annu. Rev. Neurosci. 19, 165–186 (1996).
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).
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).
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).
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).
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).
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).
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).
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).
Johnston, D. et al. Active dendrites, potassium channels and synaptic plasticity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 358, 667–674 (2003).
Magee, J.C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997).
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).
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).
Muller, W. & Bittner, K. Differential oxidative modulation of voltage-dependent K+ currents in rat hippocampal neurons. J. Neurophysiol. 87, 2990–2995 (2002).
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).
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).
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).
Bliss, T.V. & Collingridge, G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).
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).
Alkon, D.L., Lederhendler, I. & Shoukimas, J.J. Primary changes of membrane currents during retention of associative learning. Science 215, 693–695 (1982).
Turrigiano, G., Abbott, L.F. & Marder, E. Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264, 974–977 (1994).
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).
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).
Yasuda, R., Sabatini, B.L. & Svoboda, K. Plasticity of calcium channels in dendritic spines. Nat. Neurosci. 6, 948–955 (2003).
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).
Reyes, A. Influence of dendritic conductances on the input-output properties of neurons. Annu. Rev. Neurosci. 24, 653–675 (2001).
Hoffman, D.A., Sprengel, R. & Sakmann, B. Molecular dissection of hippocampal theta-burst pairing potentiation. Proc. Natl. Acad. Sci. USA 99, 7740–7745 (2002).
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).
Golding, N.L., Staff, N.P. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002).
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).
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).
Magee, J.C. & Johnston, D. Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268, 301–304 (1995).
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).
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).
Cantrell, A.R. & Catterall, W.A. Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat. Rev. Neurosci. 2, 397–407 (2001).
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).
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).
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).
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).
Markram, H., Lubke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997).
Linden, D.J. The return of the spike: postsynaptic action potentials and the induction of LTP and LTD. Neuron 22, 661–666 (1999).
Poirazi, P. & Mel, B.W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
Poirazi, P., Brannon, T. & Mel, B.W. Pyramidal neuron as two-layer neural network. Neuron 37, 989–999 (2003).
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).
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).
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).
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).
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).
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).
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.).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn1178
This article is cited by
-
Dynamic alteration of intrinsic properties of the cerebellar Purkinje cell during the motor memory consolidation
Molecular Brain (2023)
-
The plasticitome of cortical interneurons
Nature Reviews Neuroscience (2023)
-
Population imaging discrepancies between a genetically-encoded calcium indicator (GECI) versus a genetically-encoded voltage indicator (GEVI)
Scientific Reports (2021)
-
Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin
Scientific Reports (2020)
-
Stores, Channels, Glue, and Trees: Active Glial and Active Dendritic Physiology
Molecular Neurobiology (2019)