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Conservation of total synaptic weight through balanced synaptic depression and potentiation

Abstract

Memory is believed to depend on activity-dependent changes in the strength of synapses1. In part, this view is based on evidence that the efficacy of synapses can be enhanced or depressed depending on the timing of pre- and postsynaptic activity2,3,4,5. However, when such plastic synapses are incorporated into neural network models, stability problems may develop because the potentiation or depression of synapses increases the likelihood that they will be further strengthened or weakened6. Here we report biological evidence for a homeostatic mechanism that reconciles the apparently opposite requirements of plasticity and stability. We show that, in intercalated neurons of the amygdala, activity-dependent potentiation or depression of particular glutamatergic inputs leads to opposite changes in the strength of inputs ending at other dendritic sites. As a result, little change in total synaptic weight occurs, even though the relative strength of inputs is modified. Furthermore, hetero- but not homosynaptic alterations are blocked by intracellular dialysis of drugs that prevent Ca2+ release from intracellular stores. Thus, in intercalated neurons at least, inverse heterosynaptic plasticity tends to compensate for homosynaptic long-term potentiation and depression, thus stabilizing total synaptic weight.

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Figure 1: Experimental approach.
Figure 2: LTD induction produces heterosynaptic LTP.
Figure 3: LTP induction produces heterosynaptic LTD.
Figure 4: Ca2+ release from intracellular stores is required for the conservation of total synaptic weight.

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Acknowledgements

This work was supported by the National Science Foundation, the Canadian Institutes of Health Research and the Center for Molecular and Behavioral Neuroscience of Rutgers University. We thank Dr E. J. Lang for comments on the manuscript.

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Correspondence to Denis Paré.

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The authors declare that they have no competing financial interests.

Supplementary information

41586_2003_BFnature01530_MOESM1_ESM.pdf

Supplementary Information: contains two tables summarizing the average changes in response amplitude seen in various conditions (control, AP5, BAPTA, RR and CPA) at the induction site and heterosynaptic sites. (PDF 5 kb)

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Royer, S., Paré, D. Conservation of total synaptic weight through balanced synaptic depression and potentiation. Nature 422, 518–522 (2003). https://doi.org/10.1038/nature01530

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