 |
The Journal of Neuroscience, October 25, 2006, 26(43):11001-11013; doi:10.1523/JNEUROSCI.1749-06.2006
Previous Article | Next Article 
Cellular/Molecular
Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity
Thomas Nevian and
Bert Sakmann
Department of Cell Physiology, Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany
Correspondence should be addressed to Thomas Nevian at his present address: Institute for Physiology, Bern University, Bühlplatz 5, CH-3012 Bern, Switzerland. Email: nevian{at}pyl.unibe.ch
Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca2+ ([Ca2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca2+]i transients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca2+]i was uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca2+]i transients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca2+]i levels. Activation of voltage-dependent Ca2+ channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca2+]i transient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca2+-dependent induction of LTP.
We conclude that the volume-averaged peak elevation of [Ca2+]i in spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca2+ sensors in spines control the induction of spike-timing-dependent synaptic plasticity.
Key words: LTP; LTD; synaptic plasticity; calcium; two-photon microscopy; spine; spike-timing-dependent plasticity; mGluR; NMDAR
Received April 25, 2006;
revised Sept. 13, 2006;
accepted Sept. 14, 2006.
Correspondence should be addressed to Thomas Nevian at his present address: Institute for Physiology, Bern University, Bühlplatz 5, CH-3012 Bern, Switzerland. Email: nevian{at}pyl.unibe.ch
This article has been cited by other articles:

|
 |

|
 |
 
F. W. Johenning, P. S. Beed, T. Trimbuch, M. H. K. Bendels, J. Winterer, and D. Schmitz
Dendritic Compartment and Neuronal Output Mode Determine Pathway-Specific Long-Term Potentiation in the Piriform Cortex
J. Neurosci.,
October 28, 2009;
29(43):
13649 - 13661.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Zilberter, C. Holmgren, I. Shemer, G. Silberberg, S. Grillner, T. Harkany, and Y. Zilberter
Input Specificity and Dependence of Spike Timing-Dependent Plasticity on Preceding Postsynaptic Activity at Unitary Connections between Neocortical Layer 2/3 Pyramidal Cells
Cereb Cortex,
October 1, 2009;
19(10):
2308 - 2320.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Holbro, A. Grunditz, and T. G. Oertner
Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses
PNAS,
September 1, 2009;
106(35):
15055 - 15060.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. Frey, R. Sprengel, and T. Nevian
Activity Pattern-Dependent Long-Term Potentiation in Neocortex and Hippocampus of GluA1 (GluR-A) Subunit-Deficient Mice
J. Neurosci.,
April 29, 2009;
29(17):
5587 - 5596.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. D. Acker and S. D. Antic
Quantitative Assessment of the Distributions of Membrane Conductances Involved in Action Potential Backpropagation Along Basal Dendrites
J Neurophysiol,
March 1, 2009;
101(3):
1524 - 1541.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Fox
Experience-dependent plasticity mechanisms for neural rehabilitation in somatosensory cortex
Phil Trans R Soc B,
February 12, 2009;
364(1515):
369 - 381.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Kano, T. Ohno-Shosaku, Y. Hashimotodani, M. Uchigashima, and M. Watanabe
Endocannabinoid-Mediated Control of Synaptic Transmission
Physiol Rev,
January 1, 2009;
89(1):
309 - 380.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Galvan, E. Calixto, and G. Barrionuevo
Bidirectional Hebbian Plasticity at Hippocampal Mossy Fiber Synapses on CA3 Interneurons
J. Neurosci.,
December 24, 2008;
28(52):
14042 - 14055.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Corlew, D. J. Brasier, D. E. Feldman, and B. D. Philpot
Presynaptic NMDA Receptors: Newly Appreciated Roles in Cortical Synaptic Function and Plasticity
Neuroscientist,
December 1, 2008;
14(6):
609 - 625.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
J. R. Pugh and I. M. Raman
Mechanisms of Potentiation of Mossy Fiber EPSCs in the Cerebellar Nuclei by Coincident Synaptic Excitation and Inhibition
J. Neurosci.,
October 15, 2008;
28(42):
10549 - 10560.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. N. Sarkar, R.-Q. Huang, S. M. Logan, K. D. Yi, G. H. Dillon, and J. W. Simpkins
Estrogens directly potentiate neuronal L-type Ca2+ channels
PNAS,
September 30, 2008;
105(39):
15148 - 15153.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Shen, M. Flajolet, P. Greengard, and D. J. Surmeier
Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity
Science,
August 8, 2008;
321(5890):
848 - 851.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. P. J. de Kock and B. Sakmann
High frequency action potential bursts (>= 100 Hz) in L2/3 and L5B thick tufted neurons in anaesthetized and awake rat primary somatosensory cortex
J. Physiol.,
July 15, 2008;
586(14):
3353 - 3364.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Huang, H. Yasuda, A. Sarihi, and T. Tsumoto
Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice
J. Neurosci.,
July 9, 2008;
28(28):
7074 - 7083.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Saha and S. M. Dudek
Action Potentials: To the Nucleus and Beyond
Experimental Biology and Medicine,
April 1, 2008;
233(4):
385 - 393.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser
Dendritic Excitability and Synaptic Plasticity
Physiol Rev,
April 1, 2008;
88(2):
769 - 840.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Egger, T. Nevian, and R. M. Bruno
Subcolumnar Dendritic and Axonal Organization of Spiny Stellate and Star Pyramid Neurons within a Barrel in Rat Somatosensory Cortex
Cereb Cortex,
April 1, 2008;
18(4):
876 - 889.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-i. Tanaka, Y. Horiike, M. Matsuzaki, T. Miyazaki, G. C. R. Ellis-Davies, and H. Kasai
Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines
Science,
March 21, 2008;
319(5870):
1683 - 1687.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. L. Bloodgood and B. L. Sabatini
Regulation of synaptic signalling by postsynaptic, non-glutamate receptor ion channels
J. Physiol.,
March 15, 2008;
586(6):
1475 - 1480.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Pawlak and J. N. D. Kerr
Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity
J. Neurosci.,
March 5, 2008;
28(10):
2435 - 2446.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Farries and A. L. Fairhall
Reinforcement Learning With Modulated Spike Timing Dependent Synaptic Plasticity
J Neurophysiol,
December 1, 2007;
98(6):
3648 - 3665.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Buchanan and J. R. Mellor
The development of synaptic plasticity induction rules and the requirement for postsynaptic spikes in rat hippocampal CA1 pyramidal neurones
J. Physiol.,
December 1, 2007;
585(2):
429 - 445.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Fuenzalida, D. Fernandez de Sevilla, and W. Buno
Changes of the EPSP Waveform Regulate the Temporal Window for Spike-Timing-Dependent Plasticity
J. Neurosci.,
October 31, 2007;
27(44):
11940 - 11948.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Hashimotodani, T. Ohno-Shosaku, M. Watanabe, and M. Kano
Roles of phospholipase Cbeta and NMDA receptor in activity-dependent endocannabinoid release
J. Physiol.,
October 15, 2007;
584(2):
373 - 380.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-t. Lu, C.-y. Li, J.-P. Zhao, M.-m. Poo, and X.-h. Zhang
Spike-Timing-Dependent Plasticity of Neocortical Excitatory Synapses on Inhibitory Interneurons Depends on Target Cell Type
J. Neurosci.,
September 5, 2007;
27(36):
9711 - 9720.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Gasparini, A. Losonczy, X. Chen, D. Johnston, and J. C. Magee
Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons
J. Physiol.,
May 1, 2007;
580(3):
787 - 800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Cui, B. E. Bernier, M. T. Harnett, and H. Morikawa
Differential Regulation of Action Potential- and Metabotropic Glutamate Receptor-Induced Ca2+ Signals by Inositol 1,4,5-Trisphosphate in Dopaminergic Neurons
J. Neurosci.,
April 25, 2007;
27(17):
4776 - 4785.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Canepari, M. Djurisic, and D. Zecevic
Dendritic signals from rat hippocampal CA1 pyramidal neurons during coincident pre- and post-synaptic activity: a combined voltage- and calcium-imaging study
J. Physiol.,
April 15, 2007;
580(2):
463 - 484.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. C. Gerkin, P.-M. Lau, D. W. Nauen, Y. T. Wang, and G.-Q. Bi
Modular Competition Driven by NMDA Receptor Subtypes in Spike-Timing-Dependent Plasticity
J Neurophysiol,
April 1, 2007;
97(4):
2851 - 2862.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|