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I have a basic knowledge of how neural networks work. A potential difference is created that forces sodium, potassium, chloride, and calcium ions to flow which carries an electrical signal to the end of a synapse. From there, the presynaptic neuron releases neurotransmitters creating a potential difference to the postsynaptic neuron.

What I don't understand yet are the mechanics of which neurotransmitter will be released. Do the vesicles of each type of neurotransmitter have an energy threshold? If yes, when the highest energy threshold of a vesicle is achieved, does this mean all the other vesicles will release the encapsulated neurotransmitters?

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  • $\begingroup$ The vesicles are associated with a calcium-sensitive membrane complex composed of quite a few proteins, some details here. (I'll try to detail an answer when time permits) $\endgroup$
    – CKM
    Commented Dec 23, 2015 at 23:31
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    $\begingroup$ Have you heard of SNARE proteins? $\endgroup$
    – Stan Shunpike
    Commented Dec 24, 2015 at 9:34

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The release of neurotransmitters is a very specific type of SNARE mediated exocytosis. The action potential from the influx of sodium propagates along the axon and reaches the axon terminal, containing the calcium channels. This causes the calcium cations (ions) to travel down the electrochemical gradient. The Ca2+ then binds to a protein. The vesicles containing the neurotransmitter called synaptotagmin (Ca sensors), would cause conformational changes leading to the formation of a SNARE complex. Some good animations can be seen here and here.

Regarding whether there is an energy threshold: there is a threshold on the amount of Calcium needed to cause the activation of synaptotagmin, as with all types of SNAREs.

See this article: http://www.pnas.org/content/93/23/13327.full.pdf

Past a certain calcium threshold, all the neurotransmitter should in theory be released, but whether they cause a response would depend on the receptor and on the postsynaptic membrane, as each synapse is specific in the neurotransmitters and receptors it expresses.

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The mechanism was nicely described by FZG, I'd just like to add:

the mechanics of which neurotransmitter will be released. Do the vesicles of each type of neurotransmitter have an energy threshold?

According to this book, one such mechanism is frequency of stimulation (low frequency of action potentials) and subsequent Ca2+ distribution. With low frequency of stimulation, channels closer to the cleft are open, which means, there is higher concentration in the proximity of the cleft. With higher frequency, the concentration in the terminal bud is more equal in the proximity and further away from the synaptic membrane.

Since small neurotransmitters are usually docked closer to the synaptical membrane, low frequencies of stimulation are sufficient to increase Ca2+ in this area and release them, without changing the concentration of Ca2+ farther from the membrane, where the bigger neuropeptides are docked. They need therefore higher frequencies (as described above) to be released too. Picture.

If yes, when the highest energy threshold of a vesicle is achieved, does this mean all the other vesicles will release the encapsulated neurotransmitters?

As for the threshold, there has to be enough Ca2+ cations to activate the synaptotagmin, which is why the mechanism described above is working. However, there are few types of synaptotagmins, which have different affinities to Ca2+, which could be a another mechanism, if vesicles containing different neurotransmitter bound different synaptotagmins, but this is just a hypothesis as far as I know, maybe someone will know better here :)

The model in Fig. 3proposes that at least Syts 1, 2, 3, 6, and 7 perform complementary functions in Ca2+-triggered exocytosis whereby Ca2+ binding to each class of synaptotagmins contributes differently to triggering exocytosis

Source

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