Premium
Acute knockdown of AMPA receptors reveals a trans‐synaptic signal for presynaptic maturation
Author(s) -
Tracy Tara E,
Yan Jenny J,
Chen Lu
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.59
Subject(s) - biology , ampa receptor , gene knockdown , receptor , neuroscience , silent synapse , microbiology and biotechnology , glutamate receptor , genetics , gene
Newly formed glutamatergic synapses often lack postsynaptic AMPA‐type glutamate receptors (AMPARs). Aside from ‘unsilencing’ the postsynaptic site, however, the significance of postsynaptic AMPAR insertion during synapse maturation remains unclear. To investigate the role of AMPAR in synapse maturation, we used RNA interference (RNAi) to knockdown AMPARs in cultured hippocampal neurons. Surprisingly, loss of postsynaptic AMPARs increased the occurrence of presynaptically inactive synapses without changing the release probability of the remaining active synapses. Additionally, heterologous synapses formed between axons and AMPAR‐expressing HEK cells develop significantly fewer inactive presynaptic terminals. The extracellular domain of the AMPAR subunit GluA2 was sufficient to reproduce this effect at heterologous synapses. Indeed, the retrograde signalling by AMPARs is independent of their channel function as RNAi‐resistant AMPARs restore synaptic transmission in neurons lacking AMPARs despite chronic receptor antagonist treatment. Our findings suggest that postsynaptic AMPARs perform an organizational function at synapses that exceeds their standard role as ionotropic receptors by conveying a retrograde trans‐synaptic signal that increases the transmission efficacy at a synapse.