In Search of Memory by Eric R. Kandel
Author:Eric R. Kandel
Language: eng
Format: epub
Publisher: W. W. Norton & Company
Published: 2006-09-14T16:00:00+00:00
WITH THE TOOLS OF MOLECULAR BIOLOGY AND THE SUPPORT of the Howard Hughes Medical Institute in hand, we could now address questions about genes and memory. Since 1961 my experimental strategy had been to trap a simple form of memory in the smallest possible neural population and to use multiple microelectrodes to track the activity of participating cells. We could record signals from single sensory and motor cells for several hours in the intact animal, which was more than adequate for the study of short-term memory. But for long-term memory we needed to be able to record for one or more days. This required a new approach, so I turned to tissue cultures of the sensory and motor cells.
One cannot simply remove sensory and motor cells from adult animals and grow them, because adult cells do not survive well in culture. Instead, cells must be taken from the nervous system of very young animals and provided with an environment in which they can grow into adult cells. The crucial advance toward this goal was made by Arnold Kriegstein, an M.D.-Ph.D. student. Just before our lab moved to Columbia, Kriegstein succeeded in rearing Aplysia in the laboratory from the embryonic stage of the egg mass to adulthood, a feat that had eluded biologists for almost a century.
As it grows, Aplysia changes from a transparent, free-swimming larva that feeds on single-celled algae into a crawling, seaweed-eating juvenile slug, a small version of the adult. To achieve this radical change in body form, the larva must rest on a particular species of seaweed and be exposed to a specific chemical. No one had ever observed the metamorphosis in nature, so no one knew what the process entailed. Kriegstein observed immature Aplysia in the wild and noticed that they frequently rested on a particular species of seaweed. When he tested that seaweed by exposing larvae to it, he found that the larvae were transformed into juvenile slugs (figure 18â2). Most of us who were at Kriegsteinâs extraordinary seminar in December 1973 will not readily forget his description of how the larvae seek out a red seaweed called Laurencia pacifica, rest on it, and extract from it the chemicals needed to trigger metamorphosis. When Kriegstein showed the first pictures of the tiny juvenile snail, I remember saying to myself, âBabies are always so beautiful!â
After Kriegsteinâs discovery, we began to grow the seaweed and soon had all the juvenile animals we needed to culture cells of the nervous system. The next major taskâhow to grow individual nerve cells in culture and have them form synapsesâwas taken on by a former student of mine, Samuel Schacher, a cell biologist. With the help of two postdoctoral fellows, Schacher soon succeeded in culturing the individual sensory neurons, motor neurons, and interneurons involved in the gill-withdrawal reflex (figure 18â3).
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