Presynaptically silent synapses: Dormancy and awakening of presynaptic vesicle release

Synapses represent the main junctures of communication between neurons in the nervous system. In many neurotransmitter systems, a fraction of presynaptic terminals fails to release vesicles in response to action potential stimulation and strong calcium influx. These silent presynaptic terminals exhibit a reversible functional dormancy beyond low vesicle release probability, and dormancy status may have important implications in neural function. Recent advances have implicated presynaptic proteins interacting with vesicles downstream of cAMP and protein kinase A signaling cascades in modulating the number of these mute presynaptic terminals, and dormancy induction may represent a homeostatic neuroprotective mechanism active during pathological insults involving excitotoxicity. Interestingly, dormancy reversal may also be induced during Hebbian plasticity. Here, details of synaptic dormancy, recent insights into the molecular signaling cascades involved, and potential clinical and mechanistic implications of this form of synaptic plasticity are described.