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Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity

An Erratum to this article was published on 01 December 2000

Abstract

To examine how functional circuits are established in the brain, we studied excitatory transmission in early postnatal hippocampus. Spontaneous neural activity was sufficient to selectively deliver GluR4-containing AMPA receptors (AMPA-Rs) into synapses. This delivery allowed non-functional connections to transmit at resting potentials and required NMDA receptors (NMDA-Rs) but not CaMKII activation. Subsequently, these delivered receptors were exchanged with non-synaptic GluR2-containing AMPA-Rs in a manner requiring little neuronal activity. The enhanced transmission resulting from this delivery and subsequent exchange was maintained for at least several days and required an interaction between GluR2 and NSF. Thus, this sequence of subunit-specific trafficking events triggered by spontaneous activity in early postnatal development may be crucial for initial establishment of long-lasting functional circuitry.

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Figure 1: Expression of endogenous and recombinant GluR4 during early hippocampal development.
Figure 2: Synaptic delivery of recombinant GluR4.
Figure 3: Spontaneous activity delivers GluR4-GFP into synapses.
Figure 4: Delivery of GluR4-GFP to silent synapses.
Figure 5: Delivery of endogenous GluR4 into synapses.
Figure 6: Exchange of synaptic GluR4-GFP with endogenous GluR2-containing receptor maintains potentiated transmission.
Figure 7: Maintenance of enhanced transmission depends on interactions between GluR2 and NSF.

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Acknowledgements

We thank Song-Hai Shi for help in cloning GluR2-GFP and GluR3-GFP constructs, Nancy Dawkins-Pisani and Tamara Howard for technical assistance, and H. Cline, J. Huang, Z. Mainen, E. Ruthazer and members of the Malinow laboratory for comments and discussions. This study was supported by the NIH, the Alzheimer's Association and the NARSAD Foundation.

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Zhu, J., Esteban, J., Hayashi, Y. et al. Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity. Nat Neurosci 3, 1098–1106 (2000). https://doi.org/10.1038/80614

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