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Distributed synaptic modification in neural networks induced by patterned stimulation

Nature volume 401, pages 792–796 (1999)Cite this article

Abstract

Activity-dependent changes in synaptic efficacy or connectivity are critical for the development1, signal processing2 and learning and memory functions3,4,5,6 of the nervous system. Repetitive correlated spiking of pre- and postsynaptic neurons can induce a persistent increase or decrease in synaptic strength, depending on the timing of the pre- and postsynaptic excitation7,8,9,10,11,12,13. Previous studies on such synaptic modifications have focused on synapses made by the stimulated neuron. Here we examine, in networks of cultured hippocampal neurons, whether and how localized stimulation can modify synapses that are remote from the stimulated neuron. We found that repetitive paired-pulse stimulation of a single neuron for brief periods induces persistent strengthening or weakening of specific polysynaptic pathways in a manner that depends on the interpulse interval. These changes can be accounted for by correlated pre- and postsynaptic excitation at distant synaptic sites, resulting from different transmission delays along separate pathways. Thus, through such a ‘delay-line’ mechanism, temporal information coded in the timing of individual spikes14,15,16,17 can be converted into and stored as spatially distributed patterns of persistent synaptic modifications in a neural network.

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Figure 1: Polysynaptic pathways in a network of cultured hippocampal neurons.
Figure 2: Pathway remodelling induced by repetitive paired-pulse stimulation (PPS).
Figure 3: Pathway remodelling induced by correlated excitation through transmission delay.
Figure 4: Modifications of remote excitatory synapses by correlated spiking.

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Acknowledgements

We thank X. Wang for culture preparations and B. Berninger, W. Kristan, L. Zhang, A. Schinder and S. Andersen for helpful discussions and comments on the manuscript. Supported by grants from NIH (M.P.) and a President's Postdoctoral Fellowship from the University of California and a training grant from NIH (G.B.).

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  1. Department of Biology, University of California at San Diego, La Jolla, 92093-0357, California, USA

    Guo-qiang Bi & Mu-ming Poo

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  1. Guo-qiang Bi
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Correspondence to Guo-qiang Bi.

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Bi, Gq., Poo, Mm. Distributed synaptic modification in neural networks induced by patterned stimulation. Nature 401, 792–796 (1999). https://doi.org/10.1038/44573

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