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Now THIS Is a Synapse

Every time I read about the synapse, the all-important junction between two neurons, the cartoon above pops into my head. It shows the gist of how a synapse works: An electrical pulse enters the cell on the left and activates those little blue balls, called vesicles, to release their chemical contents, called neurotransmitters. The neurotransmitters spill out into the space between the cells, called the cleft, and activate those blue rectangles, called ion channels. The channels trigger the cell on the right to fire its own electrical pulse, or action potential, and this message travels on to the next cell. It’s pretty neat. Our brains are full of trillions of synapses, each with the capability of converting an electrical signal into a chemical one and back again.

My doodle is conceptually useful for understanding many neuroscience studies. It helped me visualize, for example, how researchers record the messages of brain cells, and how the synapse plays a role in developmental disorders, and how the firing patterns of all of these synapses provide our brains with a sophisticated coding scheme.

The downside of the cartoon synapse is that it gives a false impression. It makes it seem as if the synapse is simple and all figured out, when actually it’s mostly baffling. I was reminded of its complexity by a study published in today’s issue of Science. Researchers in Germany used an array of techniques — including Western blot, mass spectrometry, electron microscopy, and super-resolution fluorescence microscopy — to create a three-dimensional model of a typical synapse in the adult rat brain. You’ll see in the video below that their new model doesn’t look much like my drawing:

To get the most out of the video, click on the white arrows in the lower right hand corner, which will expand it to full screen. The video shows the synaptic bouton, which is the left part of my cartoon. The glowing red “active zone” at the bottom is where the neurotransmitters get dumped into the cleft. Toward the end of the video you can see a close-up of a vesicle releasing its contents and then being recycled by the cell.

The model shows some 300,000 individual proteins, and remember — they’re all hanging out at a single synapse! The image below shows a cross-section of the bouton; each color corresponds to a different kind of protein. The active zone is again the glowing red part at the bottom.

Wilhelm et al., Science 2014

(Click to enlarge)

More often than not, neuroscientists (and therefore, science writers covering neuroscience) tend to focus on a single protein at a time. For instance, I’ve written about that green guy, parvalbumin, because in certain neurons the protein seems to trigger high-frequency brain waves that have been linked to cognition. And that red SNAP-25 has been linked to ADHD, and the yellow VDAC has been proposed as a good target for chemotherapy drugs.

The only way to untangle this complex picture is to focus on its individual components, figuring out one piece at a time. But the next time you read about one of those pieces, recall how it fits into the whole, and be wowed.

22 thoughts on “Now THIS Is a Synapse

  1. double WOW!!! that video is beautiful, amazing, and almost every superlative on a dictionary. The detail is incredible.

  2. Great story! Wonderful to learn about the amazing complexity and to catch a glimpse of how much more there is to learn!

  3. Unfortunately, the video can’t be put into full screen mode on my tablet (Nexus 7), making it very hard to view.

  4. Unfotunately it will not show full screen on a first gen iPad. As a matter of fact I can’t seem to even sign in on the first gen iPad lately either.
    I am wondering if it is just mine or are there other iPad users having the same problem.
    It allows me to comment on items like this where you are not already signed in though. Very puzzling!!!

  5. Fantastic – however “focus on its individual components, figuring out one piece at a time” might well be a dead end – it may be the interactions that hold the key rather than any single element….

  6. @Dwayne LaGrou- the expand arrows on the bottom right wouldn’t work on my iPad 2, but the regular expand gesture does. Try that?

    Also WOW. Just wow. And some more wow. Wow.

  7. Those captions are really informative and allow you to skip forward very quickly. I like them better than voiceover.

  8. The miracle begins when one considers that a single sperm contains a small brain ready to be used once it becomes fertilized. The whole procedure from sperm construction till birth contains so much extraordinary evolution that it is mind blowing. I don’t understand how all this was self evolved in such a perfect way through years.

  9. Thanks for that, Virginia. For once, the superlative ‘awesome’ is appropriate – particularly as it’s an incomprehensible illustration of the mechanism which is trying to work out the incomprehensible mechanism :o)

  10. Non-neuroscience stegosaurs like me will not hope to really understand the function of this anatomical structure in much better detail than the cartoon at top shows. Presumably the receptor proteins at right in the cartoon change their shape or conformation when the transmitter molecules bind to them. Beginners will need to learn about both graded and action potential in a neuron before they can understand how the receiving cell is ultimately induced to “fire” it’s own action potential. A key difference is that action potential is “all or nothing,” once fired, it propagates across the entire cell membrane, including down the axons. Graded potential remains localized around the portion of membrane near the synapse that was stimulated. This means graded potentials can be summed, and if the sum hits a threshold, firing happens. The large bouton image seems to show the inner surface of the membrane in one of the two cells involved at a synaptic junction. I don’t know whether it is the “sender” cell or the “receiver.” But tubulin, the red things that look like coil springs, belongs inside–it is in all body cells, I think. Fascinating.

  11. Sorry for double-commenting here, and sorry my last comment isn’t too clear. But I like John Forrest’s remark above (May 31), and V. Hughes’ reply. I think both the top-down ‘systems’ and bottom-up ‘components’ approaches are need to understand something. The systems approach is like the cartoon at top, giving a fast overview of function. The actual system IS made of its components, however, and you must understand these before you can claim to understand the system. The systems approach of course risks teleology–imposing design goals when neurons don’t come with owner’s manuals. The components approach risks getting lost in a warren of seemingly unrelated details, making some kind of conceptual framework necessary. Correct me if I’m wrong on this.

  12. Note to Constantine:

    You’re right, you don’t understand how evolution, aka “change”, works. As every molecule combines with others, they combine their experience to form new organs which allow them to behave in more ways than they used to. That’s how everything ORGANICALLY GROWS, Constantine. The mind that is a product of such change also includes imagination, which in a very simplistic, superficial, even childish way, that is where you get your belief in gods/a god, which we made up in our minds to solve problems when we’re uneducated, which waved her, oh excuse me, “his” magic wand and just made it be! As if the complex world is really no more than the doings of a busy stick-figure cartoon.

  13. for “Apple” folk… the video player is from vimeo.com please check there for tips on work-arounds for your apple device and browser combinations. It will help you here and on many sites.
    Virginia – thanks for helping people understand how complex and wonderful cells really are…

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