A Neuroscience Field Guide: Vagusstoff

Vaguwhaa?? Vagusstoff literally means “stuff from the vagus nerve”. This is from the days where scientists gave things really imaginative names, and if you were German, you could combine several words to come up with some official sounding term like “Bitsöfbraininajähr”. But back to Vagusstoff. Vagusstoff (make sure you use a strong Germanic pronunciation when saying it) is actually the neurotransmitter acetylcholine, before it was known to be acetylcholine, or rather when it was thought to be something else.

Back in the early days of neuroscience, like in the 1920’s, folks already knew electrical impulses formed the basis of signaling in the nervous system. But there was some debate whether chemicals might also mediate part of this signaling. This was the start of what later became the “war of the soups vs. the sparks”. The soup camp favored a chemical mode of communication between brain cells, while the spark camp said neurons were electrically coupled to each other. Enter physiologist Otto Loewi.  Loewi had been preoccupied by a specific question about how the heart worked.  The heart is innervated by two main nerves, the vagus nerve and the sympathetic nerve. If you activate the sympathetic nerve, the heart rate accelerates, but if you activate the vagus, then the heart rate slows. What was puzzling to him was that if both nerves were electrically coupled to the heart, how could they lead to opposite effects? Perhaps, he thought, the nerves are releasing some “stuff” that then differentially modulates the heart rate.

Loewi designed the following experiment. He took a frog heart and kept it in a chamber with media. Then he stimulated the shit out of the vagus nerve using a series of electric shocks. This caused the heart rate to slow. He took a second frog heart in another chamber, and this heart was denervated (ie. had both nerves removed). He then extracted some media surrounding the first heart and added it to the chamber containing the denervated heart. If a chemical was released by the vagus which caused the heart to slow, then this chemical should be present in the media around the heart and should also cause slowing of the second heart. And that is exactly what happened, when he added media from the stimulated heart to the chamber containing the second heart, the second heart also slowed, confirming his hypothesis. Since he couldn’t come up with a better name for this stuff released by the vagus, he called it Vagusstoff.

Loewi did several variants of the same experiment and published his findings in 1921 in a paper entitled “Über humorale Übertragbarkeit der Herznervenwirkung. I.” Fun stuff. Anyway, Vagusstoff turned out to be the same thing as a chemical previously discovered by pharmacologist Sir Henry Dale which was known as acetylcholine. It also turned out that the stuff leaking out of the sympathetic nerve was the neurotransmitter norepinephrine. Thanks to Loewi’s experiments it was finally accepted that communication between neurons could be chemical, and both shared a Nobel prize in 1936. The war of the soups and sparks raged on for several years, and when the dust settled it turned out that the nervous system contains both chemical and electrical synapses, but that’s another story.


Speaking of stories, there’s a crazy one about Loewi. According to neuroscience lore, Loewi first had his idea for his experiment in the middle of the night in a dream. But after he went back to sleep and awoke the next morning, he forgot what the stupid experiment was supposed to be. The next night he had the same dream and this time he rose in the middle of the night and ran to the lab in his pajamas to extract some frog hearts. By the morning he had discovered synaptic transmission.

So the lesson? I’m not sure. Something about going to the lab in your pajamas — or something.


Further Reading

Otto Loewi’s Nobel Lecture.

Sir Henry Dale’s Nobel Lecture.

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2 Responses to A Neuroscience Field Guide: Vagusstoff

  1. Zen Faulkes says:

    The story isn’t crazy lore. Loewi recounts this story in “From the Workshop of Discoveries.” This is online here (page 33): http://kuscholarworks.ku.edu/dspace/bitstream/1808/6348/1/upk.workshop_of_discoveries.pdf

    I was always struck by the fact that Loewi had his dream in Easter Sunday. I can imagine Loewi’s kids:

    “Daddy, daddy, I found an Easter egg!”

    “SHUT UP! Daddy’s trying to remember something that might win him the Nobel prize!”

  2. tideliar says:

    Awesome story. I remember my PhD advisor opening his lecture series on electrphysiology in grad school by recounting this story. Had a room full of bio400 and bio500 students completely transfixed 🙂

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