Lindau Nobel Laureate Meeting: Neuroscientists’ little chemical helpers

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lindau_nobel_logoThere is a lot of chemistry going on in the brain. But neuroscience, too, heavily depends on sophisticated chemicals. Today Erwin Neher, medicine Nobel laureate of 1991, introduced over 500 young researchers from all over the world to the subtleties of synapse research with caged compounds and indicator dyes.

Neurons in the brain communicate via electrical signals, the action potentials. But at the contact point, called synapses, there is a small gap that the action potential cannot cross. Here, chemicals take over. Neurotransmitters are released, migrate across the gap and induce a new action potential.

The neurotransmitters are stored in vesicles within the synapse. Upon a signal those membrane bubbles connect with the outer Membrane and release their chemical content. But what kind of signal? Physiologists suspected Calcium-ions.

To find out if this was true, researchers needed a way to measure calcium concentrations with high spatial and temporal resolution, while at the same time detect the signal of neurotransmitter release. A very difficult task, because normal synapses are rather small. There is, fortunately, an exception to this rule: It’s called the Calyx of Held, a giant synapse in the auditory cotex, where, as Neher explained, such measurements were possible.

That’s where the aforementioned sophisticated chemistry is required. There are special dyes that show a concentration-dependent fluorescence in the presence of Calcium.By using those dyes, scientists showed that a local increase in Calcium concentration indeed precedes the release of Neurotransmitters. But that’s no proof.

Fortunately there are compounds called Ca-DNM. They contain Calcium and again a fluorescent domain. But now the fluorescence is quenched by the cage. But with light of the right wavelenght, the cage opens and the Calcium is released, together with the fluorecent compound.

Now researchers could observe fluorescence opt the caged compound and directly afterwards detected the signal of neurotransmitter release: Calcium ions indeed induce fusion of vesicles with the outer membrane. Knowing this, even more sophisticated experiments revealed dose-response curves of this particular interactions and gave clues of the calcium affinity of the involved receptor.

But still the exact mechanism of neurotransmitter release remains unknown, explained Neher. He is, however, optimistic, that new, specialised chemistry will eventually solve the puzzle.

Update: PZ Myers was there, too, and his story is rather better than this one. And he wrote it after having lots of beer. I should try that too…
Btw, it’s ‘Erwin’, And the calcium really should be Ca2+. Ca2 would be quite disrupting to live cells.

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