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The Journal of Neuroscience, December 15, 1998, 18(24):10464-10472

Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type

Guo-qiang Bi and Mu-ming Poo

Department of Biology, University of California at San Diego, La Jolla, California 92093

In cultures of dissociated rat hippocampal neurons, persistent potentiation and depression of glutamatergic synapses were induced by correlated spiking of presynaptic and postsynaptic neurons. The relative timing between the presynaptic and postsynaptic spiking determined the direction and the extent of synaptic changes. Repetitive postsynaptic spiking within a time window of 20 msec after presynaptic activation resulted in long-term potentiation (LTP), whereas postsynaptic spiking within a window of 20 msec before the repetitive presynaptic activation led to long-term depression (LTD). Significant LTP occurred only at synapses with relatively low initial strength, whereas the extent of LTD did not show obvious dependence on the initial synaptic strength. Both LTP and LTD depended on the activation of NMDA receptors and were absent in cases in which the postsynaptic neurons were GABAergic in nature. Blockade of L-type calcium channels with nimodipine abolished the induction of LTD and reduced the extent of LTP. These results underscore the importance of precise spike timing, synaptic strength, and postsynaptic cell type in the activity-induced modification of central synapses and suggest that Hebb's rule may need to incorporate a quantitative consideration of spike timing that reflects the narrow and asymmetric window for the induction of synaptic modification.

Key words: synaptic modification; plasticity; hippocampal neurons; LTP; LTD; correlated-activity; spike timing; spiking; Hebb's rule; Hebbian; target specificity; cell culture


Copyright © 1998 Society for Neuroscience  0270-6474/98/182410464-09$05.00/0


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Y.-D. Zhou, C. D. Acker, T. I. Netoff, K. Sen, and J. A. White
Increasing Ca2+ transients by broadening postsynaptic action potentials enhances timing-dependent synaptic depression
PNAS, December 27, 2005; 102(52): 19121 - 19125.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
E. Fino, J. Glowinski, and L. Venance
Bidirectional Activity-Dependent Plasticity at Corticostriatal Synapses
J. Neurosci., December 7, 2005; 25(49): 11279 - 11287.
[Abstract] [Full Text] [PDF]


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Cereb CortexHome page
R. A. Koene and M. E. Hasselmo
An Integrate-and-fire Model of Prefrontal Cortex Neuronal Activity during Performance of Goal-directed Decision Making
Cereb Cortex, December 1, 2005; 15(12): 1964 - 1981.
[Abstract] [Full Text] [PDF]


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ScienceHome page
B. L. Bloodgood and B. L. Sabatini
Neuronal Activity Regulates Diffusion Across the Neck of Dendritic Spines
Science, November 4, 2005; 310(5749): 866 - 869.
[Abstract] [Full Text] [PDF]


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Cereb CortexHome page
S. D. Faulkner, V. Vorobyov, and F. Sengpiel
Limited Protection of the Primary Visual Cortex from the Effects of Monocular Deprivation by Strabismus
Cereb Cortex, November 1, 2005; 15(11): 1822 - 1833.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
D. V. Buonomano
A Learning Rule for the Emergence of Stable Dynamics and Timing in Recurrent Networks
J Neurophysiol, October 1, 2005; 94(4): 2275 - 2283.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
F. J Veredas, F. J Vico, and J.-M. Alonso
Factors determining the precision of the correlated firing generated by a monosynaptic connection in the cat visual pathway
J. Physiol., September 15, 2005; 567(3): 1057 - 1078.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
D. T. Blake, F. Strata, R. Kempter, and M. M. Merzenich
Experience-Dependent Plasticity in S1 Caused by Noncoincident Inputs
J Neurophysiol, September 1, 2005; 94(3): 2239 - 2250.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
S. Ge and J. A. Dani
Nicotinic Acetylcholine Receptors at Glutamate Synapses Facilitate Long-Term Depression or Potentiation
J. Neurosci., June 29, 2005; 25(26): 6084 - 6091.
[Abstract] [Full Text] [PDF]


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NeuroscientistHome page
H. Yao and Y. Dan
Synaptic Learning Rules, Cortical Circuits, and Visual Function
Neuroscientist, June 1, 2005; 11(3): 206 - 216.
[Abstract] [PDF]


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J. Neurophysiol.Home page
J. E. Rubin, R. C. Gerkin, G.-Q. Bi, and C. C. Chow
Calcium Time Course as a Signal for Spike-Timing-Dependent Plasticity
J Neurophysiol, May 1, 2005; 93(5): 2600 - 2613.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
J. D. Cohen and M. A. Castro-Alamancos
Skilled Motor Learning Does Not Enhance Long-Term Depression in the Motor Cortex In Vivo
J Neurophysiol, March 1, 2005; 93(3): 1486 - 1497.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
J. Xu, N. Kang, L. Jiang, M. Nedergaard, and J. Kang
Activity-Dependent Long-Term Potentiation of Intrinsic Excitability in Hippocampal CA1 Pyramidal Neurons
J. Neurosci., February 16, 2005; 25(7): 1750 - 1760.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
H. Z. Shouval and G. Kalantzis
Stochastic Properties of Synaptic Transmission Affect the Shape of Spike Time-Dependent Plasticity Curves
J Neurophysiol, February 1, 2005; 93(2): 1069 - 1073.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
A. Starovoytov, J. Choi, and H. S. Seung
Light-Directed Electrical Stimulation of Neurons Cultured on Silicon Wafers
J Neurophysiol, February 1, 2005; 93(2): 1090 - 1098.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
K. Schon, M. E. Hasselmo, M. L. LoPresti, M. D. Tricarico, and C. E. Stern
Persistence of Parahippocampal Representation in the Absence of Stimulus Input Enhances Long-Term Encoding: A Functional Magnetic Resonance Imaging Study of Subsequent Memory after a Delayed Match-to-Sample Task
J. Neurosci., December 8, 2004; 24(49): 11088 - 11097.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
S. Fujisawa, N. Matsuki, and Y. Ikegaya
Chronometric readout from a memory trace: gamma-frequency field stimulation recruits timed recurrent activity in the rat CA3 network
J. Physiol., November 15, 2004; 561(1): 123 - 131.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
I. Aradi and G. Maccaferri
Cell Type-Specific Synaptic Dynamics of Synchronized Bursting in the Juvenile CA3 Rat Hippocampus
J. Neurosci., October 27, 2004; 24(43): 9681 - 9692.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
A. K. Lee and M. A. Wilson
A Combinatorial Method for Analyzing Sequential Firing Patterns Involving an Arbitrary Number of Neurons Based on Relative Time Order
J Neurophysiol, October 1, 2004; 92(4): 2555 - 2573.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
S. J. Judge and M. E. Hasselmo
Theta Rhythmic Stimulation of Stratum Lacunosum-Moleculare in Rat Hippocampus Contributes to Associative LTP at a Phase Offset in Stratum Radiatum
J Neurophysiol, September 1, 2004; 92(3): 1615 - 1624.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
L. M. Frank, G. B. Stanley, and E. N. Brown
Hippocampal Plasticity across Multiple Days of Exposure to Novel Environments
J. Neurosci., September 1, 2004; 24(35): 7681 - 7689.
[Abstract] [Full Text] [PDF]



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