Explorers of the Black Box by Susan Allport

Author:Susan Allport
Language: eng
Format: epub, mobi
ISBN: 9781504034104
Publisher: Open Road Distribution
Published: 2016-05-30T16:00:00+00:00

SIX

The Manifold Neuron

Inserting a microelectrode into a nerve cell, according to Juan Acosta-Urquidi, a postdoctoral student in Alkon’s lab in the early eighties, is like sticking a broomstick into a balloon.

Or shimmying into a tight pair of pants, says Greg Clark, a young neurophysiologist working with Kandel.

It is how neurophysiologists spend much of their time, an everyday procedure, but one still far too difficult for scientists to take wholly for granted.

To neurophysiologists of the 1940s, sticking a finely drawn glass tube through the membrane of a nerve cell in order to record the electrical activity of the inside of a cell was a radical act. No one knew if the cell could survive such treatment, if it might not, instead, deflate, burst like a balloon, or somehow lose its ability to transmit electrical signals. It was a big surprise to everybody when the cells into which the first microelectrodes were stuck didn’t fall apart. On the contrary, their membranes seemed to form a kind of seal around the glass intruder, then go about their business. After a period of hours, the membrane tended to become increasingly leaky to ions, but until then the cells transmitted action potential after action potential as though no one were watching.

At first, neurophysiologists thought that only the largest nerve cells would be able to tolerate a microelectrode inside of them. But in the years since the first landmark experiments with microelectrodes, in 1946, scientists have succeeded in inserting into increasingly tiny cells microelectrodes that are not that much finer than the ones used originally. It is now fairly commonplace to record from inside one of the tiny neurons in a mammalian brain, a feat unthinkable forty years ago.

Intracellular recording has always been technically difficult. In some ways, it is even more difficult today than when it was first tried since most of the easy experiments on the big cells have already been done, and scientists are now attempting ever more arduous maneuvers. Sticking one cell with a microelectrode is difficult; sticking four different cells in the same ganglion with four different electrodes, then maintaining those cells and those electrodes over the course of a long experiment, is almost impossible. Neurophysiologists do it, but at the rate of only about one successful experiment for every week of trying.

“Nine-tenths of what we do is a dismal failure,” Bob Hawkins, an investigator in Kandel’s lab has told me.

“Every step of an experiment adds to the probability of failure,” says Jack Byrne, the electrical engineer who converted to neurophysiology after observing the goings-on in Kandel’s lab. “There are so many variables. First, you have to have a healthy animal, then a good dissection and good electrodes. Then you have to find the cells you want and impale them without damaging either the cells or the electrodes. Finally, you have to be able to hold that cell, record from it, and do whatever else the experiment requires—changing solutions, squirting in neurotransmitters, dyes, and inhibitors, voltage clamping, et cetera. I’d say we probably average about one successful experiment a week.

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