Abstract
Whereas the regenerative nature of action potential conduction in axons has been known since the late 1940s, neuronal dendrites have been considered as passive cables transferring incoming synaptic activity to the soma. The relatively recent discovery that neuronal dendrites contain active conductances has revolutionized our view of information processing in neurons. In many neuronal cell types, sodium action potentials initiated at the axon initial segment can back-propagate actively into the dendrite thereby serving, for the dendrite, as an indicator of the output activity of the neuron. In addition, the dendrites themselves can initiate action-potential-like regenerative responses, so-called dendritic spikes, that are mediated either by the activation of sodium, calcium, and/or N-methyl-D-aspartate receptor channels. Here, we review the recent experimental and theoretical evidence for a role of regenerative dendritic activity in information processing within neurons and, especially, in activity-dependent synaptic plasticity.
Similar content being viewed by others
References
Artola A, Singer W (1993) Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci 16:480–487
Bear MF, Abraham WC (1996) Long-term depression in hippocampus. Annu Rev Neurosci 19:437–462
Bi GQ, Poo MM (1998) Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci 18:10464–10472
Bischofberger J, Jonas P (1997) Action potential propagation into the presynaptic dendrites of rat mitral cells. J Physiol (Lond) 504:359–365
Buzsaki G, Kandel A (1998) Somadendritic backpropagation of action potentials in cortical pyramidal cells of the awake rat. J Neurophysiol 79:1587–1591
Buzsaki G, Penttonen M, Nadasdy Z, Bragin A (1996) Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo. Proc Natl Acad Sci USA 93:9921–9925
Callaway JC, Ross WN (1995) Frequency-dependent propagation of sodium action potentials in dendrites of hippocampal CA1 pyramidal neurons. J Neurophysiol 74:1395–1403
Cash S, Yuste R (1998) Input summation by cultured pyramidal neurons is linear and position-independent. J Neurosci 18:10–15
Cash S, Yuste R (1999) Linear summation of excitatory inputs by CA1 pyramidal neurons. Neuron 22:383–394
Chen WR, Midtgaard J, Shepherd GM (1997) Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells. Science 278:463–467
Cho K, Aggleton JP, Brown MW, Bashir ZI (2001) An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat. J Physiol (Lond) 532:459–466
Connor JA, Petrozzino J, Pozzo-Miller LD, Otani S (1999) Calcium signals in long-term potentiation and long-term depression. Can J Physiol Pharmacol 77:722–734
Conti R, Lisman J (2002) A large sustained Ca2+ elevation occurs in unstimulated spines during the LTP pairing protocol but does not change synaptic strength. Hippocampus 12:667–679
Coombs JS, Curtis DR, Eccles JC (1957) The interpretation of spike potentials of motoneurones. J Physiol (Lond) 139:198–231
Cormier RJ, Greenwood AC, Connor JA (2001) Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold. J Neurophysiol 85:399–406
Dan Y, Poo MM (2004) Spike timing-dependent plasticity of neural circuits. Neuron 44:23–30
Djurisic M, Zecevic D (2005) Imaging of spiking and subthreshold activity of mitral cells with voltage-sensitive dyes. Ann N Y Acad Sci 1048:92–102
Fatt P (1957) Sequence of events in synaptic activation of a motoneurone. J Neurophysiol 20:61–80
Fuortes MG, Frank K, Becker MC (1957) Steps in the production of motoneuron spikes. J Gen Physiol 20:735–752
Goldberg J, Holthoff K, Yuste R (2002) A problem with Hebb and local spikes. Trends Neurosci 25:433–435
Golding NL, Spruston N (1998) Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons. Neuron 21:1189–1200
Golding NL, Kath WL, Spruston N (2001) Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites. J Neurophysiol 86:2998–3010
Golding NL, Staff NP, Spruston N (2002) Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418:326–331
Hansel C, Artola A, Singer W (1997) Relation between dendritic Ca2+ levels and the polarity of synaptic long-term modifications in rat visual cortex neurons. Eur J Neurosci 9:2309–2322
Häusser M, Stuart G, Racca C, Sakmann B (1995) Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15:637–647
Häusser M, Spruston N, Stuart GJ (2000) Diversity and dynamics of dendritic signaling. Science 290:739–744
Hebb DO (1949) The organization of behaviour. Wiley, New York
Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat Methods 2:932–940
Helmchen F, Svoboda K, Denk W, Tank DW (1999) In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nat Neurosci 2:989–996
Hirsch JA, Alonso JM, Reid RC (1995) Visually evoked calcium action potentials in cat striate cortex. Nature 378:612–616
Hoffman DA, Magee JC, Colbert CM, Johnston D (1997) K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387:869–875
Holthoff K (2004) Regenerative dendritic spikes and synaptic plasticity. Curr Neurovasc Res 1:381–387
Holthoff K, Kovalchuk Y, Yuste R, Konnerth A (2004) Single-shock LTD by local dendritic spikes in pyramidal neurons of mouse visual cortex. J Physiol (Lond) 560:27–36
Holthoff K, Kovalchuk Y, Konnerth A (2005) Bidirectional single-shock synaptic plasticity induced by dendritic spikes in cortical pyramidal cells. Soc Neurosci Abstr 162:3
Hounsgaard J, Yamamoto C (1979) Dendritic spikes in Purkinje cells of the guinea pig cerebellum studied in vitro. Exp Brain Res 37:387–398
Ismailov I, Kalikulov D, Inoue T, Friedlander MJ (2004) The kinetic profile of intracellular calcium predicts long-term potentiation and long-term depression. J Neurosci 24:9847–9861
Jefferys JG (1979) Initiation and spread of action potentials in granule cells maintained in vitro in slices of guinea-pig hippocampus. J Physiol (Lond) 289:375–388
Johnston D, Magee JC, Colbert CM, Cristie BR (1996) Active properties of neuronal dendrites. Annu Rev Neurosci 19:165–186
Kamondi A, Acsady L, Buzsaki G (1998) Dendritic spikes are enhanced by cooperative network activity in the intact hippocampus. J Neurosci 18:3919–3928
Köster HJ, Sakmann B (1998) Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. Proc Natl Acad Sci USA 95:9596–9601
Larkum ME, Rioult MG, Lüscher HR (1996) Propagation of action potentials in the dendrites of neurons from rat spinal cord slice cultures. J Neurophysiol 75:154–170
Larkum ME, Kaiser KM, Sakmann B (1999) Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials. Proc Natl Acad Sci USA 96:14600–14604
Lisman J (1989) A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci USA 86:9574–9578
Lisman J, Spruston N (2005) Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity. Nat Neurosci 8:839–841
Losonczy A, Magee JC (2006) Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. Neuron 50:291–307
Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305:719–721
Magee JC (2000) Dendritic integration of excitatory synaptic input. Nat Rev Neurosci 1:181–190
Magee JC, Johnston D (1995) Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268:301–304
Magee JC, Johnston D (1997) A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275:209–213
Malenka RC (1991) The role of postsynaptic calcium in the induction of long-term potentiation. Mol Neurobiol 5:289–295
Malenka RC, Lancaster B, Zucker RS (1992) Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation. Neuron 9:121–128
Mank M, Reiff DF, Heim N, Friedrich MW, Borst A, Griesbeck O (2006) A FRET-based calcium biosensor with fast signal kinetics and high fluorescence change. Biophys J 90:1790–1796
Markram H, Lübke J, Frotscher M, Sakmann B (1997) Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275:213–215
Miesenböck G (2004) Genetic methods for illuminating the function of neural circuits. Curr Opin Neurobiol 14:395–402
Migliore M, Hoffman DA, Magee JC, Johnston D (1999) Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. J Comput Neurosci 7:5–15
Miyakawa H, Kato H (1986) Active properties of dendritic membrane examined by current source density analysis in hippocampal CA1 pyramidal neurons. Brain Res 399:303–309
Neveu D, Zucker RS (1996a) Long-lasting potentiation and depression without presynaptic activity. J Neurophysiol 75:2157–2160
Neveu D, Zucker RS (1996b) Postsynaptic levels of [Ca2+]i needed to trigger LTD and LTP. Neuron 16:619–629
Nevian T, Sakmann B (2004) Single spine Ca2+ signals evoked by coincident EPSPs and backpropagating action potentials in spiny stellate cells of layer 4 in the juvenile rat somatosensory barrel cortex. J Neurosci 24:1689–1699
Palmer LM, Stuart GJ (2006) Site of action potential initiation in layer 5 pyramidal neurons. J Neurosci 26:1854–1863
Pan E, Colbert CM (2001) Subthreshold inactivation of Na+ and K+ channels supports activity-dependent enhancement of back-propagating action potentials in hippocampal CA1. J Neurophysiol 85:1013–1016
Pockberger H (1991) Electrophysiological and morphological properties of rat motor cortex neurons in vivo. Brain Res 539:181–190
Poirazi P, Mel BW (2001) Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29:779–796
Polsky A, Mel BW, Schiller J (2004) Computational subunits in thin dendrites of pyramidal cells. Nat Neurosci 7:621–627
Ramón y Cajal S (1891) Significación fisiológica de las expansiones protoplásmicas y nerviosas de la sustancia gris. Rev Cienc Med Barcel 22:23
Ramón y Cajal S (1904) La textura del sistema nerviosa del hombre y los vertebrados, primera edicion. Moya, Madrid
Rathenberg J, Nevian T, Witzemann V (2003) High-efficiency transfection of individual neurons using modified electrophysiology techniques. J Neurosci Methods 126:91–98
Regehr W, Kehoe JS, Ascher P, Armstrong C (1993) Synaptically triggered action potentials in dendrites. Neuron 11:145–151
Reyes A (2001) Influence of dendritic conductances on the input-output properties of neurons. Annu Rev Neurosci 24:653–675
Richardson TL, Turner RW, Miller JJ (1987) Action-potential discharge in hippocampal CA1 pyramidal neurons: current source-density analysis. J Neurophysiol 58:981–996
Roberts PD, Bell CC (2002) Spike timing dependent synaptic plasticity in biological systems. Biol Cybern 87:392–403
Schiller J, Schiller Y (2001) NMDA receptor-mediated dendritic spikes and coincident signal amplification. Curr Opin Neurobiol 11:343–348
Schiller J, Schiller Y, Stuart G, Sakmann B (1997) Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons. J Physiol (Lond) 505:605–616
Schiller J, Major G, Köster HJ, Schiller Y (2000) NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 404:285–289
Sjostrom PJ, Nelson SB (2002) Spike timing, calcium signals and synaptic plasticity. Curr Opin Neurobiol 12:305–314
Sjostrom PJ, Turrigiano GG, Nelson SB (2001) Rate, timing, and cooperativity jointly determine cortical synaptic plasticity. Neuron 20:1149–1164
Spencer WA, Kandel ER (1961) Electrophysiology of hippocampal neurons. IV. Fast prepotentials. J Neurophysiol 24:272–285
Spruston N, Schiller Y, Stuart G, Sakmann B (1995) Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268:297–300
Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci USA 100:7319–7324
Stuart G, Häusser M (1994) Initiation and spread of sodium action potentials in cerebellar Purkinje cells. Neuron 13:703–712
Stuart GJ, Häusser M (2001) Dendritic coincidence detection of EPSPs and action potentials. Nat Neurosci 4:63–71
Stuart GJ, Sakmann B (1994) Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367:69–72
Stuart G, Schiller J, Sakmann B (1997a) Action potential initiation and propagation in rat neocortical pyramidal neurons. J Physiol (Lond) 505:617–632
Stuart G, Spruston N, Sakmann B, Häusser M (1997b) Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci 20:125–131
Svoboda K, Denk W, Kleinfeld D, Tank DW (1997) In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385:161–165
Svoboda K, Helmchen F, Denk W, Tank DW (1999) Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo. Nat Neurosci 2:65–73
Tsodyks M (2002) Spike-timing-dependent synaptic plasticity—the long road towards understanding neuronal mechanisms of learning and memory. Trends Neurosci 25:599–600
Turner RW, Meyers DE, Richardson TL, Barker JL (1991) The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons. J Neurosci 11:2270–2280
Urban NN, Barrionuevo G (1998) Active summation of excitatory postsynaptic potentials in hippocampal CA3 pyramidal neurons. Proc Natl Acad Sci USA 95:11450–11455
Vetter P, Roth A, Häusser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85:926–937
Wang SS, Denk W, Häusser M (2000) Coincidence detection in single dendritic spines mediated by calcium release. Nat Neurosci 3:1266–1273
Waters J, Helmchen F (2004) Boosting of action potential backpropagation by neocortical network activity in vivo. J Neurosci 24:11127–11136
Waters J, Larkum M, Sakmann B, Helmchen F (2003) Supralinear Ca2+ influx into dendritic tufts of layer 2/3 neocortical pyramidal neurons in vitro and in vivo. J Neurosci 23:8558–8567
Waters J, Schäfer A, Sakmann B (2005) Backpropagating action potentials in neurones: measurement, mechanisms and potential functions. Prog Biophys Mol Biol 87:145–170
Wei DS, Mei YA, Bagal A, Kao JP, Thompson SM, Tang CM (2001) Compartmentalized and binary behavior of terminal dendrites in hippocampal pyramidal neurons. Science 293:2272–2275
Yang SN, Tang YG, Zucker RS (1999) Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J Neurophysiol 81:781–787
Yuste R, Tank DW (1996) Dendritic integration in mammalian neurons, a century after Cajal. Neuron 16:701–716
Yuste R, Majewska A, Cash SS, Denk W (1999) Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis. J Neurosci 19:1976–1987
Zecevic D (1996) Multiple spike-initiation zones in single neurons revealed by voltage-sensitive dyes. Nature 381:322–325
Zhang LI, Tao HW, Holt CE, Harris WA, Poo M (1998) A critical window for cooperation and competition among developing retinotectal synapses. Nature 395:37–44
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Holthoff, K., Kovalchuk, Y. & Konnerth, A. Dendritic spikes and activity-dependent synaptic plasticity. Cell Tissue Res 326, 369–377 (2006). https://doi.org/10.1007/s00441-006-0263-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-006-0263-8