Sunday, June 01, 2014

Virginia Hughes - Now THIS Is a Synapse (3-D Video Modeling of a Synapse)

This is a cool article from Virginia Hughes at Phenomena: Only Human, a National Geographic blog. Hughes presents a video (embedded below, but you'll need to go to Vimeo to see it, just follow the link) that provides a 3-D view of a synapse in an adult rat brain.

We tend to think, and the psycho-pharma folks would have us believe, that we have the synapse all figured out, as Hughes drawing above might suggest. However, in the model created in the video, there are at least 300,000 individual proteins represented, and that is only in one synapse of the billions possible in a human brain.

What we currently know about the human brain, or brains in general, is dwarfed by that which we do not know.

Now THIS Is a Synapse

by Virginia Hughes

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:

synapse video from Virginia Hughes on Vimeo.

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.

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