Complexin...not so inconsequential anymore

Researchers at MIT's Picower Institute for Learning and Memory may have found the key to controlling how the brain is wired while studying the bursts of activity that occur after communication between neurons.

First, I will give an overview of neural communication. Neural cells communicate with each other at a synapse, which is the point of contact between the cells at which signals are transmitted. The action potential stimulates the input cell (presynaptic) to release neurotransmitters. These neurotransmitters travel across the synaptic cleft and bind to neurotransmitter receptors on the receiving (postsynaptic) cell. However, the action of the neurotransmitter needs to be controlled so that the cell is not continually activated.

That is where this new research, conducted by Sarah Huntwork and J Troy Littleton, comes in. These scientists have identified a molecule, called complexin, which acts as a gatekeeper to help control the release of neurotransmitters. As it turns out, a few cells will continue to release neurotransmitters even after the major electrical stimulus has passed. They call these events "minis", which are regulated by complexin. However, they have discovered that in the absence of complexin, these minis can occur without regulation, and when they do, it can lead to rewiring of the brain and synaptic growth.

So what does this mean in terms of neurological diseases? The activity of complexin can be controlled, and if properly regulated, may allow synaptic growth to be stimulated and rewiring of the brain to occur.

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Lua, did you forget you posted that; do you need a complexin supplement? ;-)

Just kidding - this is fascinating stuff; thanks for posting. The whole area of cellular differentiation in the CNS and the factors leading to rewiring (and the ceasing thereof) are of major importance if we are to understand degenerative brain disease and abnormalities of brain development (including learning disabilities). It's already a hugely complex field, but at least in the case of Fragile X syndrome, there are glimmerings that treatments may become available - a thought that was felt to be ridiculous just a few short *weeks* ago. Also, we need to know more about these pesky stem cells, which is an argument for *more* research, not less, of course.

Oh man, I shamefully stopped reading Littleton's work when I stopped working on synaptotagmins. need to check this out, stat.

Thanks for the heads up, PZ.

By minimalist (not verified) on 20 Sep 2007 #permalink

Thanks for the heads up, PZ.

Erm: "Posted ... by Lua Yar"

More fascinating details this week in Science Daily about what's happening on the other side of the cleft too.

The researchers employed fluorescent imaging studies that revealed that dynamin-3 concentrates at the endocytic zone and couples itself to another protein, called Homer. Homer was known to attach to the postsynaptic density. Molecular studies revealed dynamin-3 can latch onto Homer by forming chains of dynamin proteins that bridge the distance between the endocytic zone and the postsynaptic density.

Ehlers noted that one of his group's key experiments showed that the endocytic machinery uncoupled from the postsynaptic density when dynamin-3 was knocked out in the neurons. "Even though our molecular analysis showed quite clearly that dynamin-3 functions as a connector, it was really surprising that disrupting dynamin-3 so completely caused this uncoupling," said Ehlers. "This gives a tool to do experiments nobody has done before--exploring what happens when you no longer have recycling going on right next to the postsynaptic density."

"There are still a lot of molecular details of the dynamin-3 mechanism we don't understand," said Ehlers. "But we now have the tools to disrupt it selectively, to further explore its function. Furthermore, we can now manipulate the pools of receptors and ask interesting questions about how availability of receptors affects the ability of the synapse to undergo critical plastic change in its strength," he said.

Wow. I didn't even notice until I got to the comments that it wasn't PZ doing the writing. I'm impressed. (Lua, have you been noticing any growths resembling tentacles lately?)

This is fascinating stuff to this here semi-educated layman.

This is fascinating material. Post more!

so...

shall we call this evidence of Irreducible Complexin?

(sorry, but somebody had to).

Tatarize, the sarcasm came through loud and clear on the second attempt - but perhaps only because I did rush out and buy it when it came out (or in 1997, to be precise). Not that I regret it - it was my first year of full-time paid employment after being a student for decades, so the odd bit of wastage is only to be expected.

By John Scanlon, FCD (not verified) on 20 Sep 2007 #permalink

Uncontrolled neural rewiring is probably not a good idea. If it were, we likely wouldn't have developed a physiological pathway to limit it in the first place.

By Caledonian (not verified) on 20 Sep 2007 #permalink

I actually learned about somethine like this today in class!

In other news, "synapse" backwards is "espanys"

Good post. More please Lua.

So there is a certain tension between normal functioning of neurons and synaptic growth. Not exactly what I would call "nice" :-P, but understandable and interesting.

I'm sorry, but actually I found a more fascinating item on development today, the press release describing results on how nuclear membrane forms during mitosis. I have a vague memory of the disassembling-assembling hypothesis and the machinery it required to evenly divide and reform the nuclear membrane.

But what actually happens makes more sense, a natural folding and binding of ER tubules around the chromatin. Perhaps PZ can get some evo-devo mileage out of that, or at least find some analogy to embryonic tissue layers.

By Torbjörn Larsson, OM (not verified) on 20 Sep 2007 #permalink

That's some really great writing. I was seriously pulled in. I was hoping there would be more after the fold. With pictures. I don't mean you didn't "do enough", though. I'm telling you that what you have is really good and I want more. :-)

What I understand of this sounds very cool, but I must admit it's a little over my head. A pretty picture might help and a little bit of "in layman's terms".

Anyway, great post (and still nothing to rip you on).

So there is a certain tension between normal functioning of neurons and synaptic growth. Not exactly what I would call "nice" :-P, but understandable and interesting.

I'm sorry, but actually I found a more fascinating item on development today, the press release describing results on how nuclear membrane forms during mitosis. I have a vague memory of the disassembling-assembling hypothesis and the machinery it required to evenly divide and reform the nuclear membrane.

But what actually happens makes more sense, a natural folding and binding of ER tubules around the chromatin. Perhaps PZ can get some evo-devo mileage out of that, or at least find some analogy to embryonic tissue layers.

By Torbjörn Larsson, OM (not verified) on 20 Sep 2007 #permalink