Active Zone

Introduction to Active Zone

The active zone has been considered as a key delivery system for the release of neurotransmitters. Among them, different kinds of synapses have been found to link different neurons. Normally, a synapse consists of various types of presynaptic regions to help store the vesicles in neurotransmitters or their receptors. The materials in the neurotransmitters vesicles will be released into the synaptic cleft to stimulate neurotransmitter release signalings when the action potential reaches the presynaptic. Afterward, certain signaling can promote specific neurotransmitters transfer from gaps to the postsynaptic neurons, and trigger the activation of neurotransmitter receptors. Moreover, previous studies have shown that the active zone in the presynaptic region also contains many presynaptic membranes and various cell-matrix proteins. Proteins in the active zone can attach synaptic vesicles to the presynaptic membrane and mediate synaptic vesicle fusion, allowing the accurate and rapid release of neurotransmitters upon the arrival of action potentials.

Fig.1 Molecular architecture of the active zone. (Ovsepian, 2011)

Functions of Active Zone

In the past few years of studies, many studies have demonstrated that the action potential can reach speeds of up to 500 Hertz, synaptic transmission would need to be very fast to match. As a result, the time error among the arrival of the action potential, the release of the neurotransmitter, as well as the release window must be limited to a few milliseconds. To achieve it, the active zone has been identified that is responsible for controlling the best speed and timing of the synaptic transmission process. Meanwhile, a variety of active zone-specific proteins, such as RIMs, Munc13s, or CAST/ERCs, have been discovered and mediating several steps of active zone function, including Ca²⁺ dependent fusion. Moreover, recent reports have revealed that the active zone plays an important role in mediating the secretory activity. In general, the release of the synaptic transmitter is restricted to a diameter of 200-300 nm area of the active zone. This restriction property is critical for establishing a rapid signal propagation neural network and avoiding unnecessary diffusion or the loss of neuronal information.

Besides, the active zone can dynamically regulate the level and the efficiency of neurotransmitter release. The active zone release level is usually very low, but it can be modulated over a wide range. The number of vesicles available for fusion is limited in the active zone, and each regulatory action leads to the loss of the fused vesicles, which is also the principal mechanism of synaptic inhibition.

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Reference

1. Ovsepian, S. V.; et al. Dendritic SNAREs add a new twist to the old neuron theory. Proceedings of the National Academy of Sciences. 2011, 108(48): 19113-19120.