AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses

Ping Li, Geoffrey A. Kerchner, Carlo Sala, Feng Wei, James E. Huettner, Morgan Sheng, Min Zhuo

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor-PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain.

Original languageEnglish
Pages (from-to)972-977
Number of pages6
JournalNature neuroscience
Volume2
Issue number11
DOIs
StatePublished - Nov 1999

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