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The key role for the NSF, in neuroscience support, has to be to search out and support the development of new materials for research of this kind. It is not good enough to support “more of the same” indefinitely, that is, the same kind of research that has been going on in the field, indefinitely.

NSF's particular specialty has been in being free, scientifically free, to find new and better ways to solve difficult problems. We anticipate this extraordinary progresss to continue and with very significant consequences for scientists and non-scientists alike. Thank you.

[The prepared statement of Dr. Willows follows:]

STATEMENT OF
DR. A.0. DENNIS WILLOWS

DIRECTOR
NEUROBIOLOGY PROGRAM
NATIONAL SCIENCE FOUNDATION

BEFORE THE
SUB COMMITTEE ON SCIENCE AND TECHNOLOGY
U.S. HOUSE OF REPRESENTATIVES

FEBRUARY 20, 1980

Mr. Chairman and Members of the Committee:

Neurobiology, the study of the brain mechanisms of behavior is a relatively new science. It has undergone an extraordinary amount of growth in the last ten years with an influx of scientists from physics, chemistry, psychology, biology and medicine. The primary reason for the growth however, is the success that has already been achieved in understanding the relationship between brain and behavior, and further the sense in the minds of many scientists, that there are a number of very important developments on the near horizon.

The influx of scientists from diverse scientific fields inco neurobiology has been a major source of strength. It has meant that work has progressed on a very broad front and a variety of techniques and approaches have been used. In particular, it has resulted in the development of a number of simple model systems which have facilitated the study of difficult brain-behavior problems but in experimental circumstances which are very favorable to progress.

Let me cite a number of examples for the record and mention two in particular in a little detail:

Had tax money been used to support work on "How the squid controls its jet-like escape avior" by a biologist in the 1930's, it is likely that indignant protest might have resulted, and the matter might well have been reported as a form of entertainment in some of the press. Fortunately, the work was accomplished. Yet it is absolutely clear now, that had this attitude prevailed, and the work been discouraged, the following would not have occurred:

(1)The discovery that the squid has the largest nerve in the animal kingdom.

(11)Nobel Prize winning research showing the squid nerve 18 an ideal model for studies of how nerve electricity and transmission comes about.

(111)Development of an understanding of the basis for many nervous system disorders in all animals, humans included.

(iv)Development of an understanding of how anaesthetics work, and how venons and toxins cause their effects.

Over the past 50 years, neurobiologists have, with a considerable investment of public and private money, shown that the building blocks of brains, the nerve cells or neurons, are fundamentally similar all across the animal kingdom in terms of their electrical and chemical properties. This fact means that scientists are not forced always to solve human brain problems the "hard way", i.e. using human or even other mammalian brains. The magnitude of the difficulties of studying brains in general, and mammalian brains in particular at the cellular level can be better appreciated if a few numbers are compared:

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The message in these numbers is clear enough. Over a half million human brain cells would fit nicely inside a single large nerve cell from a slug. Where a nervous system problem involves study of cellular-level questions with the need to visualize cells, measure chemical reactions, or record from electrodes in cells, then there are real advantages in simple model systems amongst the lower animals.

One of the useful developments of recent years is the discovery that there are simple model systems in which these questions can be studied directly, all the way from the behavioral level down to the cells, membranes and molecules, in the same animal. This has come about because of the discovery that some animals have extraordinarily large brain cells--Cells so large and distinctive in color that they can be re-identified individually from animal to animal. Further, it's been possible to study the chemical, electrical and "circuit wiring" aspects of the roles of these nerve cells in relation to the behavior of the intact animal.

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Some of the gastropod mollusks, the marine slugs and their relatives have been especially important in this work, It has been found that their brains are covered by nerve cell bodies that are relatively huge in size (sometimes, Individual nerve cell bodies can be seen with the naked eye), brightly colored orange, yellow, sometimes red or black, and to the great pleasure of neurobiologists, many can be identified as individuals over and over again in different animals of the species. It has proven possible to develop techniques to record and stimulate these neurons individually in nearly intact animals, permitting quite unexpected progress in determining the "wiring diagrams" for these brains. For the same reasons of size and identifiability, these gigantic neurons have proven useful to neurochemists, who have found it possible to dissect out single nerve cells and then study the chemistry of these cells individually. As expected, their fundamental electrical and chemical properties are directly comparable to those of mammalian brain cells. This then has meant that a number of useful Insights about brain structure and function have emerged, including ideas about how circuits are wired to produce patterned behavior, and how the membrane properties of such cells contribute to their generation of impulse activity.

An additional finding from these and other studies is likely to have very important consequences in the near future. A new class of transmitter chemicals, the substances that carry messages from nerve cell to nerve cell, has been discovered. This new kind of substance is responsible for carrying signals about pain, the general sense of well-being, and may be involved in disease states, including depression, schizophrenia, and drug addiction. It is now known where these substances are produced in the mammalian brain, and even where they act. The substances called peptides, were first detected in mammals, but are now being analyzed in terms of their mode of action in a number of model systems where their cellular, and membrane effects are under careful study.

Another area of particular interest emerging from these studies of model systems, is learning and perception--Fortunately, igany lower animals seem to learn and to remember in ways which ressemble what is seen in man. And studies in mammals and such creatures as crustaceans, slugs and fish all indicate that the site of the nervous system changes which produce at least rudimentary learning, is the same in all, namely, the point of contact between nerve cells, called the synapse. It has been possible in many of these model systems to record directly from neurons in the brain while aspects of behavior proceed, thereby permitting scientists to analyze the cellular and chemical basis of the changes that accompany learning.

A key role of NSF in neurobiology has been to search cut and support the development of new tools for research of this kind. We anticipate this extraordinary progress to continue with very significant consequences for scientists and non-scientists alike.

USE OF SIMPLE ANIMAL MODELS IN NEUROBIOLOGICAL RESEARCH

As with most problems and opportunities in research, the ones in the relatively new science of the nervous system-neurosciencethat hold high interest in terms of human welfare and understanding are often the ones that are most difficult to solve. Unfortunately, what may appear to be the most direct and sensible approach to these problems, for example, by examining the human brain directly, often turns out to be very difficult, time-consuming and expensive when put to the task. On the other hand, neuroscientists are not always constrained to the direct, or "brute force" approach. There are many situations where model systems using simple animals provide quite unexpected shortcuts. Some examples of the contributions made by simple model systems to efficient progress in understanding brain functions and disorders are described below:

BRAIN CHEMICALS

The problem: What chemicals are used by the brain to carry messages from nerve cell to nerve cell? What are the chemical causes such brain centered problems as schizophrenia, drug addiction, depression, or pain?

It is now clear to neuroscientists that the basic electrical and chemical properties of the nerve cells in the brains of all animals are fundamentally identical. In this regard, a recent revolution in chemical understanding of the brain has come about as a direct consequence of the use of a range of animal model systems including snails, slugs, insects, crustaceans, worms, and leeches. A new class of chemical messengers, the peptides has been confirmed and is rapidly under development with consequences that will likely revolutionize understanding and treatment of nervous system diseases. It is also clear now that because of the cellular level source and action of these new chemicals that simple systems will play a crucial role in the further development of this research.

NERVE CIRCUITRY

The problem: How are the circuits in the brain and spinal cord that generate such activities as walking, breathing and swallowing put together?

Unlike the brains of mammals where there are tens of billions of microscopic nerve cells to contend with, some simple animals such as fishes, marine slugs, leeches, crustaceans and insects, have

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