Silent Synapse - Controversy

Controversy

The characterization of silent synapses is an ongoing field of research and there are many things about them that are not yet known. Some of what is currently accepted about the properties of silent synapses may still prove to be incorrect in whole or in part. Some controversies about silent synapses have however, been settled. For example, until recently, there were four competing hypotheses for the mechanisms of synapse silence (see Voronin et al., 2004).

• The whispering synapse hypothesis
  • a synapse that releases glutamate more slowly than normal, thus activating only high affinity NMDA receptors, but not low affinity AMPA receptors
• The low Pr synapse hypothesis
  • a synapse that is not technically silent, but appears to be so, because it has such a low presynaptic probability of release that it rarely is activated.
• The glutamate spillover hypothesis
  • a synapse that does not release its own presynaptic glutamate, but in which the postsynapse detects low concentrations of glutamate "spilling over" from neighboring synapses. Only the high affinity NMDARs, but not the low affinity AMPARs can detect this low level of glutamate
• The lack of AMPA receptor hypothesis
  • a synapse that lacks postsynaptic AMPA receptors

All four of these hypotheses had their adherents, but the first three were largely ruled out as a mechanism for synapse silence by work published since 2002 (e.g. Montgomery et al. 2002). However, recent experiments (Balland et al. 2008) have clearly established that silent synapses can be observed at brainstem synapses bearing postsynaptic AMPA receptors. This study favors the glutamate spillover hypothesis by showing that at silent synapses the glutamate concentration is reduced. At least, this study indicates that the popular hypothesis of the postsynaptic silent synapses does not apply in all systems.