Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons

Many excitatory synapses are thought to be postsynaptically 'silent', posse ssing functional NMDA but lacking functional AMPA glutamate receptors. The acquisition of AMPA receptors at silent synapses may be important in synapt ic plasticity and neuronal development. Here we characterize a possible mor phological correlate of silent synapses in cultured hippocampal neurons. In itially, most excitatory synapses contained NMDA receptors, but only a few contained detectable AMPA receptors. Synapses progressively acquired AMPA r eceptors as the cultures matured. AMPA receptor blockade increased the numb er, size and fluorescent intensity of AMPA receptor clusters and rapidly in duced the appearance of AMPA receptors at 'silent' synapses. In contrast, N MDA receptor blockade increased the size, intensity and number of NMDA rece ptor clusters and decreased the number of AMPA receptor clusters, resulting in an increase in the proportion of 'silent' synapses. These results sugge st that the number of silent synapses is regulated during development and b y changes in synaptic activity.