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Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons

Nature volume 420, pages 414–418 (2002)Cite this article

Abstract

The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability1,2. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons1,3,4,5,6. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.

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Figure 1: Overexpression of Kir2.1 in individual neurons depresses excitability.
Figure 2: Suppression of activity before synapse formation leads to a reduction in synaptic input.
Figure 3: Blocking activity uniformly using TTX equalizes synaptic inputs to Kir2.1 and control cells.
Figure 4: Suppression of excitability after synapse formation leads to a homeostatic increase in synaptic inputs.

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Acknowledgements

We thank E. Marban for the gift of the EGFP–IRES–Kir2.1 construct. We also thank the members of our laboratory for discussion. This work was supported by grants from the National Institutes of Health and the NSF. V.N.M. is a Sloan Foundation Fellow, a Pew Scholar, an EJLB Foundation Scholar and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator. J.B. is a Grable Investigator of NARSAD.

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  1. Department of Molecular & Cellular Biology, Harvard University, Cambridge, Massachusetts, 02138, USA

    Juan Burrone, Michael O'Byrne & Venkatesh N. Murthy

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  1. Juan Burrone
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Correspondence to Venkatesh N. Murthy.

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Burrone, J., O'Byrne, M. & Murthy, V. Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 420, 414–418 (2002). https://doi.org/10.1038/nature01242

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