Friday, September 28, 2018

The Lobster Book -- Eve Marder -- Charlotte Nassim -- 2018

Lessons From The Lobster: Eve Marder's Work in Neuroscience, Charlotte Nassim, c. 2018.

I began my notes on this book over at the "MillionDollarWay" blog. At that blog, search "Marder." Three entries, I believe.

From page 23:
"Could this be the place at which hormones interact, very subtly, to turn up or down the overall performance of the system without interfering at all with the actual phase relations and interactions of the system?" Astonishingly, she was already fumbling toward the idea of neuromodulation more than ten years before publishing her influential work on the phenomenon. Here, the question was posted rhetorically; at the time, she had not means of investigating it, nor did anyone else.
This is 1971; graduate work at San Diego, following undergraduate work at Brandeis.

Neuronal transmission:
  • habituation
  • facilitation
The stomatogastric ganglion: 30 neurons
The cardiac ganglion: 9 neurons

The cardiac ganglion: too simplistic; on or off; it only produces a single cycle, oscillating on or off
The stomatogastric ganglion: produces two distinct rhythms, the gastric and the pyloric, controlled by two overlapping sets of neurons. Earlier researchers had worked out which muscles the ganglion controlled.

Marder was interested from the start in what substances would be found in the ganglion's neurons, what they used as neurotransmitters. She didn't want to study connections between neurons without knowing what neurotransmitter each one used; she was convinced the message was as important as [the messenger].

In a heroically overreaching moment, young Marder decided that, for her doctoral reserach, she would find out what all the neurotransmitters used in the stomatogastric ganglion were. She had realized that knowing them all would be fundamental to understanding the mechanisms of the ganglion and how it produced its rhythmic activity. The wiring diagram on its own would not be enough.

Page 26: first mention of Henry Dale: 1914, isolated acetylcholine.

Looking back now, I think medical school would have been so much more interesting had we had an energetic, crazy, historian regale us with the history of biology at the introduction of every section. It would be completely optional whether one would attend or not; it would be held early morning or late afternoon, with tea and biscuits, etc., etc. LOL.

Long argument: whether communication between neurons was electrical or chemical. Turns out to be both.

Acetylcholine: incredibly difficult to work with -- very unstable, short-lived.

Then, Otto Loewi in 1926; his work reinvigorated Henry Dale, especially after 1929.

Henry Dale and Otto Loewi shared the Nobel Prize in 1936 for their work on "chemical neurotransmission."

That's about all Marder had to work with, I suppose.

By 1944:
  • acetylcholine
  • sympathine (renamed first noradrenaline, then norepinephrine -- in medical school in 1973, both terms were used)
  • intermedine -- now lost to science except as a constituent of borage leaves
When Marder started her research, the list of neurotransmitters had grown to about 10.

Dale's Law: page 27

Stomatogastric ganglion: fourteen different types of neurons; eventually would find that there were dozens of neurotransmitters.

Stomatograstric ganglion: interesting to Marder because of its "rhythmic output."

Why so many different neurotransmitters? From an evolutionary point of view, that seemed very, very inefficient.

Compartmented research:
Sweden: glutamate
England: acetylcholine
Boston and LA: gamma-aminobutyric acid (GABA)

"Laser uncaging": method used to map receptor distributions, page 28.

She thought wiring diagrams were insufficient to explain what was going on.

Complex feed-forward process -- page 29.

JacSue Kehoe: American researcher in Paris.


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