otto loewi neurotransmitter experiment

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History of neuroscience: Otto Loewi

Today, the knowledge that neurons communicate with one another using chemicals known as neurotransmitters is a foundational part of our understanding of brain function. We use our awareness of neurochemical transmission to design drugs, investigate the causes of disease, and improve our comprehension of behavior (e.g. through experimental methods like microdialysis ). In the first half of the twentieth century, however, the means by which neurons communicated with one another was very unclear, and many within the scientific community were convinced that communication within the nervous system was purely electrical.

The foundation for Loewi's ideas

In the early 1900s, there was a great deal of discussion and experimentation designed to determine how communication across synapses occurred. In 1902, a young German researcher named Otto Loewi took a temporary position in a laboratory at University College London . There Loewi would meet several people who were working on explaining neural transmission. One was Henry Dale , who would later go on to isolate and identify the first neurotransmitter ( acetylcholine ), and another was Thomas R. Elliot , who was a strong advocate for the idea that the nervous system utilized chemical transmission. It is likely that Loewi's discussions with Elliot first got Loewi thinking about ways to test the chemical transmission hypothesis. It would take almost two decades, however, for Loewi to dream up (literally) a viable experiment with which to do so.

Loewi's dream

According to Loewi's account, one night in 1921 he fell asleep while reading. He then had a dream in which he visualized an experiment that could put an end to the debate over how nerves communicated with one another. He woke up in the middle of the night, scribbled some notes about this potentially groundbreaking experiment, and then fell back to sleep. To his great frustration, however, when he awoke again he couldn't read the notes he had written.

The following night, he woke up at 3am after again dreaming about the experiment. This time he didn't dare risk losing his ideas to illegibility, so he rushed off to the lab to try the experiment. Loewi isolated two beating frog hearts (vertebrate cardiac muscle will continue to contract even after being removed from the body) and filled them with a saline solution. Then, he stimulated the vagus nerve in one of the hearts, a procedure that slows the heart rate. He took the saline solution from the heart whose vagus nerve he had stimulated, and applied it to the second heart. This caused the rate of the second heart to slow down.

Loewi's interpretation of these results was that there was some substance released by the vagus nerve that caused the first heart rate to slow down. The fact that the substance could then be transferred to the second heart via saline solution caused Loewi to be confident the substance was a chemical. Loewi called the putative chemical "vagusstoff" (translated from German as "vagus substance"). It took several more years before the substance was isolated by Dale and named acetylcholine .

Loewi and Dale would share the Nobel Prize in 1936 for demonstrating the importance of chemical transmission in the nervous system, and Loewi's story about the experiment coming to him in a dream would go on to be revered in the history of neuroscience. In truth, Loewi probably didn't conduct the experiment in the early morning hours as he claimed. He was known to be a storyteller with a tendency to sensationalize. According to Dale, Loewi told him he had woken up the second night and simply been fastidious in taking legible notes so he could conduct the experiment the next day. However, Loewi's version of the story is a bit more memorable, and anyone who is engaged in the daily tedium of laboratory research would have a hard time blaming Loewi for wanting to make his discovery just a little more dramatic.

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One hundred years from Otto Loewi experiment, a dream that revolutionized our view of neurotransmission

Affiliations.

• 1 Pharmacology Unit, Medical School, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain. [email protected].
• 2 Departamento de Farmacología y Terapéutica, Instituto Fundación Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.
• 3 Facultad de Medicina, Instituto de Investigación Sanitaria de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
• PMID: 34046754
• DOI: 10.1007/s00424-021-02580-9

One hundred years ago, a 4-page paper published in the Pflüger's Archiv fűr die Gesamte Physiologie des Menschen und der Tiere dramatically changed our view on synaptic transmission. The paper reported an ingenious, yet straightforward experiment made by Professor Otto Loewi in 1920 and published in 1921, which constitutes the first clear-cut proof for the chemical nature of transmission of the nerve impulse from nerve to muscle. The approach to this experiment was, however, tortuous and long.

Keywords: Acetylcholine; Adrenaline; Frog; Heart; Synapses; Synaptic transmission; Vagus nerve; Vagusstoff.

Publication types

• Historical Article
• History, 20th Century
• Neurophysiology / history*
• Synaptic Transmission*

Personal name as subject

Brain Stuff

What was otto loewi’s major contribution to neuroscience.

Answer: Otto Loewi conducted experiments on frog hearts that demonstrated that a chemical was released by nerves that can influence heart rate.

Otto Loewi (1873-1961) was a German pharmacologist. He is best known for his characterization of acetylcholine as the chemical substance that influences the rate of a heart beating in frogs, an experiment that was first published in 1921.

Prior to Loewi’s experiment, it was unclear as to whether chemical or electrical stimulation was necessary for sending signals between neurons. On one hand, it was known that electrically stimulating the nerve attached to a muscle can cause a contraction. At the same time, it was known that exposing the muscle to certain chemical substances can also cause a contraction of the muscle. However, it wasn't clear if there was a connection between these two observations. Loewi demonstrated that there was a correlation.

According to urban legend, Loewi was inspired to conduct his experiment in the middle of the night, as if the design had come to him in a dream. He leapt out of bed, and went to his laboratory, where he dissected out the hearts of two frogs. One of them was still attached to the vagus nerve, or cranial nerve IX - the cranial nerve that is responsible for parasympathetic nervous system activity. The hearts were bathed in a physiological saline solution. By stimulating the vagus nerve, Loewi observed that the heart rate slowed down, as expected.

Loewi then took some of that saline solution and bathed the second heart with that same solution. Loewi reasoned that if a chemical was released by the vagus nerve stimulation, then the second heart would respond as if it's vagus nerve was activated. The heart rate of the second heart slowed. In this experiment, he demonstrated that a chemical substance was important for the signal that is passed between the nerve and the heart muscle.

He named the chemical ”Vagusstoff”. This substance was later found to be acetylcholine. Because of his work characterizing the neurotransmitter and describing the physiological changes associated with the chemical nature of nerve signaling, he was awarded the Nobel Prize in Physiology or Medicine in 1936. This prize was shared with his friend, Sir Henry Dale.

One hundred years from Otto Loewi experiment, a dream that revolutionized our view of neurotransmission

• Pflügers Archiv's historical article
• Published: 27 May 2021
• Volume 473 , pages 977–981, ( 2021 )

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• Ricardo Borges   ORCID: orcid.org/0000-0003-3413-4392 1 &
• Antonio G. García 2 , 3  

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One hundred years ago, a 4-page paper published in the Pflüger’s Archiv fűr die Gesamte Physiologie des Menschen und der Tiere dramatically changed our view on synaptic transmission. The paper reported an ingenious, yet straightforward experiment made by Professor Otto Loewi in 1920 and published in 1921, which constitutes the first clear-cut proof for the chemical nature of transmission of the nerve impulse from nerve to muscle. The approach to this experiment was, however, tortuous and long.

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Pharmacology Unit, Medical School, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain

Ricardo Borges

Departamento de Farmacología y Terapéutica, Instituto Fundación Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain

Antonio G. García

Facultad de Medicina, Instituto de Investigación Sanitaria de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain

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Borges, R., García, A.G. One hundred years from Otto Loewi experiment, a dream that revolutionized our view of neurotransmission. Pflugers Arch - Eur J Physiol 473 , 977–981 (2021). https://doi.org/10.1007/s00424-021-02580-9

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Received : 12 April 2021

Revised : 05 May 2021

Accepted : 10 May 2021

Published : 27 May 2021

Issue Date : June 2021

DOI : https://doi.org/10.1007/s00424-021-02580-9

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