2-Minute Neuroscience: Neurotransmitter Release

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In this video, I describe the mechanisms underlying neurotransmitter release. I discuss how calcium influx is thought to play a role in mobilizing and preparing synaptic vesicles for neurotransmitter release, and I cover the hypothesized mechanism by which vesicles fuse with the cell membrane of the neuron to empty their contents into the synaptic cleft.

TRANSCRIPT:

Neurotransmitters are stored in the axon terminals of a neuron in small sac-like structures called synaptic vesicles. When an action potential travels down the neuron and reaches the axon terminal, it causes depolarization of the neuron. This change in membrane potential causes voltage-gated ion channels, which are ion channels that open in response to changes in membrane potential, to open and allow calcium to enter the cell. Calcium seems to be involved with mobilizing vesicles to prepare them for neurotransmitter release. One way this occurs is through an interaction between calcium and a protein called synapsin, which attaches vesicles to the cytoskeleton of the cell. Calcium activates an enzyme that causes synapsin to separate from the vesicles, mobilizing them for release.

After mobilization, a family of proteins called SNARE proteins are involved with getting the vesicle ready to fuse with the cell membrane of the neuron. Synaptobrevin (also called VAMP) is a SNARE protein found in the membrane of vesicles, while syntaxin and SNAP-25 are two SNARE proteins found in the cell membrane. These three proteins are thought to form a complex, which helps to bring vesicles in contact with the cell membrane, allowing the two membranes to fuse together. This process is thought to be facilitated by another protein called munc18. The role of munc18 in vesicle fusion is not completely understood, but it seems to bind to syntaxin and be necessary for fusion to occur. Another protein found in synaptic vesicles known as synaptotagmin is thought to act as a calcium sensor, which aims to promote vesicle fusion only when calcium levels in the cell are high. When the vesicle fuses with the cell membrane, it empties its contents into the synaptic cleft. After neurotransmitter release, the SNARE complex is disassembled with the help of proteins called NSF and SNAP, and the vesicle is recycled so it can be used again.

References:

Südhof TC. A molecular machine for neurotransmitter release: synaptotagmin and beyond. Nat Med. 2013 Oct;19(10):1227-31. doi: 10.1038/nm.3338.

Südhof TC, Rothman JE. Membrane fusion: grappling with SNARE and SM proteins. Science. 2009 Jan 23;323(5913):474-7. doi: 10.1126/science.1161748.
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the amount of papers i read before i came to your channel.. i wouldve been sat here for

scarl.art.
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Very elegant and clear visual explanation; thank you so much. Studying medicine really makes you realise how nature is so intricate and ingenious. Everything has a purpose and nothing is wasted.

bunclip
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I don't understand but I will try again in the future

cammychose
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I did my Master's thesis on Synapsin, way back in 1988, but got out of research then...so much more has been learned...I LOVE science...!

toAdmiller
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Excellent. This cleared up exactly the questions I had

dirklamb
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Thank you! Was explained awfully vague in my textbook

whyisgamora
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Thank you for this video! Its a good refresher for sure!

cyclomb
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Thank you. Coming from a totally different field, this helps. I'm here to simply verify some statements in a book I'm reading.

MikeTheSapien
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You beautiful man thank you so much! My confusion has vanished!!!!

UncagedWaffle
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damn didnt think you could really explain this in 2 mins and welp you did, so thank you

xianmariano
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I really found this useful. Thanks for making this! :)

KalpeshMange
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This is really great, thanks for making the video. Would you consider following up someday with what happens after neurotransmitter release (i.e. synaptic cleft, reuptake, etc)?

christianne
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This was really handy, thanks a bunch!

ellygreening
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Thank u so much
It’s really helpful !

sidrakadhim
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You should make a Udemy course all about neuroscience

idk-buse
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not me cramming 2 minutes before the test

amousenamedjay
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I take Keppra. What does that do to this process?

AgentLazarus
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Does anybody know what is the name of an enzyme that causes synapsine to separate from the vesicles?

alexbircak
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Why Calcium enters the cell at all if during depolarization, the cell is locally more positive in the inside? Doesn't that cause an accumulation of even more positive charges inside?

rokiopper
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But if calcium was less then less neurotransmition should take place but thats not what happens in tetany.. its the opposite.. why so

rjithendra