Silent synapses in the developing hippocampus: Lack of functional AMPA receptors or low probability of glutamate release?

At early developmental stages, silent synapses have been commonty found in different brain areas. These synapses are called silent because they do not respond at rest but are functional at positive membrane potentials. A wide ly accepted interpretation is that N-methyl-D-aspartate (NMDA) but not alph a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are f unctionally expressed on the subsynaptic membrane. Here we show that, in bo th CA3 and CA1 hippocampal regions, AMPA-mediated synaptic responses can be detected already at early stages of postnatal development. However, some s ynapses appear silent because of a very low probability of glutamate releas e. They can be converted into functional ones by factors that enhance relea se probability such as paired-pulse stimulation, increasing the temperature or cyclothiazide (CTZ), a drug that blocks AMPA receptor desensitization a nd increases transmitter release. Conversely, conducting synapses can be sw itched off by increasing the frequency of stimulation. Although we cannot e xclude that "latent AMPA receptors" can become functional after activity-de pendent processes, our results clearly indicate that, in the neonatal hippo campus, a proportion of glutamatergic synaptic connections are presynaptica lly rather than postsynaptically silent.