Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons

Dezhi Liao, Xiaoqun Zhang, Richard O'Brien, Michael D. Ehlers, Richard L. Huganir

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352 Scopus citations


Many excitatory synapses are thought to be postsynaptically 'silent', possessing functional NMDA but lacking functional AMPA glutamate receptors. The acquisition of AMPA receptors at silent synapses may be important in synaptic plasticity and neuronal development. Here we characterize a possible morphological correlate of silent synapses in cultured hippocampal neurons. Initially, most excitatory synapses contained NMDA receptors, but only a few contained detectable AMPA receptors. Synapses progressively acquired AMPA receptors as the cultures matured. AMPA receptor blockade increased the number, size and fluorescent intensity of AMPA receptor clusters and rapidly induced the appearance of AMPA receptors at 'silent' synapses. In contrast, NMDA receptor blockade increased the size, intensity and number of NMDA receptor clusters and decreased the number of AMPA receptor clusters, resulting in an increase in the proportion of 'silent' synapses. These results suggest that the number of silent synapses is regulated during development and by changes in synaptic activity.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
JournalNature neuroscience
Issue number1
StatePublished - Jan 1999

Bibliographical note

Funding Information:
We thank C. Doherty and J. Bernhardt for technical support and D. Bury and J. Kim for assistance in preparing the manuscript. This work was supported by the Howard Hughes Medical Institute and the National Institutes of Health (R.L.H.).


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