Putative duality of presynaptic events

The main structure in the brain responsible not only for nerve signal transmission but also for its simultaneous regulation is chemical synapse, where presynaptic nerve terminals are of considerable importance providing release of neurotransmitters. Analyzing transport of glutamate, the major excitatory neurotransmitter in the mammalian CNS, the authors suggest that there are two main relatively independent mechanisms at the presynaptic level that can influence the extracellular glutamate concentration, and so signaling, and its regulation. The first one is well-known precisely regulated compound exocytosis of synaptic vesicles containing neurotransmitters stimulated by membrane depolarization, which increases significantly glutamate concentration in the synaptic cleft and initiates glutamate signaling through postsynaptic glutamate receptors. The second one is permanent glutamate turnover across the plasma membrane that occurs without stimulation and is determined by simultaneous non-pathological transporter-mediated release of glutamate thermodynamically synchronized with uptake. Permanent glutamate turnover is responsible for maintenance of dynamic glutamate(in)/glutamate(out) gradient resulting in the establishment of a flexible extracellular level of glutamate, which can be unique for each synapse because of dependence on individual presynaptic parameters. These two mechanisms, i.e. exocytosis and transporter-mediated glutamate turnover, are both precisely regulated but do not directly interfere with each other, because they have different intracellular sources of glutamate in nerve terminals for release purposes, i.e. glutamate pool of synaptic vesicles and the cytoplasm, respectively. This duality can set up a presynaptic base for memory consolidation and storage, maintenance of neural circuits, long-term potentiation, and plasticity. Arguments against this suggestion are also considered.