The purpose of this lecture is to provide a preview of the main topics to be covered in the course.

The Edwin Smith surgical papyrus is a copy, made about 3000 years ago, of a much older original that was written in the Old Kingdom of Egypt, at the very dawn of history, 5000 years ago. Its existence illustrates a profound innovation in the evolution of animals. The human brain, uniquely among all animal brains, can create and interpret lasting symbols, and in this way can communicate across vast reaches of space and time.

This ability is unprecedented in evolution. Prior to humans, animals primarily passed on information via their genes. Humans can pass on both their genes and their ideas. However, because passing on ideas is a late evolutionary innovation, the process is not yet perfected. It is not as efficient as passing on genes, and it is certainly not as enjoyable.

The papyrus was written by a surgeon, who was describing a gaping head wound in a soldier. The wound gave the surgeon an exceptional opportunity to view a living brain. This papyrus is an icon to neuroscientists. It contains the oldest known reference in any written language to the brain. The hieroglyphics that refer to the brain, which are reproduced on p. 3 of your text, are literally translated as the marrow of the skull.

In spite of its historical significance, the papyrus contains no special secrets. For all of their wisdom, the Egyptians had no conception of the brain's importance, and embalmers routinely drained it out through the nostrils and discarded it, while keeping for mummification such internal organs as the liver and the spleen.

This course is designed to be a first course in the Neurosciences for students with a Biology background, or a second course for students with a Psychology or other social science background. This course should prepare you for more advanced courses in the neurosciences, including Neurobiology 200.

The central question this course considers is:

How can a chunk of tissue think? 

What is the nature of the mind?
The cognitive sciences attempt to answer that question.

Can a machine be designed that will think?
Artificial intelligence attempts to answer that question.  Since computers presently differ strikingly from brains in their material and design, we can expect different processes, but these may be instructive.  As an analogy, consider birds and airplanes.  Both can fly, but there are enormous difference in strategy.  The ability of computer programs to simulate mental processes that we consider specifically human can astonish.  In a recent essay in Science, and a beautiful reflection on the essay [required] by Natalie Angier, even aspects of creativity can be simulated.  As summarized by Angier: 

"The notion of creative thinking as amenable to parsing and replication is both cheering and disheartening: cheering because it means that just about anybody can learn to do it at least passably well, and disheartening for showing, once again, that even genius is so much meat in motion." (italics added).

What is the nature of the chunk of tissue?
 Neurosciences attempts to answer that question.  This course will exam how the brain is being investigated and what we are learning about its operations.

What are the neurosciences? The fundamental approach of the neurosciences is biological: neuroscience is a subset of biology. It is not an area of biology, like molecular biology or population biology, but instead cuts across all areas to focus on a major organ system. It brings to bear upon that system insights from every level of biological thought.

The central strategy of the neurosciences is the same as that of biology--it is to understand that our brains, and the minds to which they give rise, have evolved. It is therefore essential to study a wide range of organisms if we are truly to understand the human brain. Furthermore, as we shall see, some organisms, often the simpler ones, are ideal for illuminating particular problems in brain function.

Once an evolutionary perspective is adopted, it follows naturally that the ultimate function of nervous systems is seen to be the production of behavior, which in turn is a major mechanism for ensuring survival.

Biologists are behaviorists because they have learned that evolution selects for adaptive behavior. Evolution is indifferent to thought without action, but behavior itself is extremely sensitive to selection pressure.

Therefore, the relation of the neurosciences to the behavioral and cognitive sciences is that both seek ways to understand how brains give rise to thought and action--thought being important to the extent it shapes behavior.

The cellular-connectionistic approach.
Tactics: how do neuroscientists design their experiments? Although the neurosciences use a great range of techniques, the field is presently unified by what might be called the cellular-connectionistic approach. This approach says that the brain, although vast in size, needs to be studied at the level of individual neurons if its mechanisms are to be understood. That proposal is based on evidence that the 10 billion or more nerve cells in our brain are highly individualistic in their properties and that they make highly precise and perhaps uniquely patterned connections with other cells. 

A vivid illustration of how the brain can be directly influenced with surprising effect is shown in this illustration of a living cortex of a conscious patient, who has been prepared for surgery with a local anesthetic. The surgeon's task is to find and remove diseased tissue that is causing epileptic seizures, while doing minimal damage to the brain. This kind of surgery was pioneered by Wilder Penfield at McGill University, and is still carried out today, although at only a few centers.

The brain is covered by this tough sheet of dura mater that is peeled back to expose the surface. Tiny electrical currents can then be applied to various parts of the cortex. Depending on the spot stimulated, patients may blink, raise their arms, see flashing lights, hear music, or experience a vivid emotional experience, as though experiencing a long lost memory! This method is called brain stimulation, and is an important technique for localizing brain function.

But how does the brain work? Given that one part of the brain mediates vision and another audition, how do they actually do what they do?

One of the most important distinctions I would like you to appreciate is the distinction between research that tells us where something happens and research that tells us how it happens: the distinction between localization and mechanism.

However, knowing where things happen in the brain is an essential beginning.

A midsagittal section of the head lets us see some of the major areas of the brain: the cerebral hemispheres, the diencephalon, the midbrain, the pons and cerebellum, and the spinal cord. We will come to appreciate the distinctions among these areas in later lectures, and will also learn that almost all functional systems cut across most or all of these areas, wiring them together.

All of the wonders of this exposed cortex are hidden-- it is like unwrapping a computer but not looking inside the case. The ancients guessed correctly that looking more closely would help.

In a closer view of the cortex, the convolutions of the brain, called sulci and gyri, are apparent. Ancients thought these were important, but we now think these convolutions have little significance.  They are merely a way of crumpling up a large planar sheet to fit within the skull.  We must look at cellular structure to learn about the brain.  However, normal, untreated brain tissue is almost transparent.

In a tiny piece of cortex in which about 1% of the neurons have been turned black with a special stain (Golgi stained cortex), you can see that neurons are quite elaborate. The cell body gives rise to many find projections -- some of which branch repeatedly -- others of which run as fine threads for many centimeters.

How can the behavior of such complex cells be studied in living animals?

One way is called microelectrode recording. A microelectrode is like a tiny microphone that can detect the electrical signals produced by a single nerve cell. I can't emphasize too strongly the great importance of being able to listen to the activity of neurons individually. We have learned with this technique that neurons are remarkably individualized, and that trying to study their averaged behavior can obscure an understanding of the meaning of their messages, just as you may learn very little by listening to the buzz of conversation in a large room.  Extracellular microelectrodes enable us to get very close to a single neuron, and eavesdrop on what it is saying to other neurons.

How do we know which particular neuron we were listening to? And, is there any way to know what a neuron is thinking, as well as what it is saying?

One of the most powerful methods for studying single neurons is a method called intracellular microelectrode recording. In this method, a microscopically small, hollow glass needle is pushed through the membrane of the cell. The inside of the hollow glass needle is filled with a concentrated salt solution that allows investigators to record the subthreshold electrical activity of the cell--activity that in many neurons is analogous to "thinking" about what they will do.

Intracellular recording has another benefit--it allows us to fill the neuron with a marker to make it visible. By this means, we get a precise correspondence between what the cell looks like, where it is located, and its electrical activity. This neuron has been injected with a highly fluorescent marker via an intracellular microelectrode. We filled this cell in my laboratory at Stanford, and although it is from an invertebrate, it has all of the main features of a typical vertebrate neuron, including this long axon for sending signals to other cells.

Suppose we follow the output signal of the neuron along the axon. The axon may enter the densely tangled cables of the central nervous system, or it may leave the nervous system and go to muscles.

Consider a bundle of nerve axons as they course across muscle fibers. It is a remarkable fact that all of the information that enters and leaves our brains travels as digital electrical signals in the long, thin processes of nerve cells called axons. Those digital signals can now be recorded from nerve cells inside living brains.

When you move any part of your body, from a wink of the eye to kicking a football, you activate your muscles by sending signals to them along nerves. Fortunately, the electrical signaling process used by nerve cell axons to conduct information has common properties in every animal studied, from jellyfish and worms to humans, and also in both the peripheral nerves and the neurons deep within the brain. We will focus on how this process works, because once we understand nerve impulse conduction we will be well positioned for a deeper and more satisfying understanding of brain function.

The process of conducting information along a cable is drastically altered when the signal reaches the end of the cable, where it must be transmitted to another cell. The process of cell to cell information transmission, much more complex and differentiated than impulse conduction, takes place at special structures called synapses.

A single synapse made by a motor neuron onto a muscle fiber is an ideal place to study neurotransmission. When a nerve impulse reaches this area, it causes the release of a chemical, called a neurotransmitter, that excites the muscle fiber and causes it to contract. You can see that these synapses are large and isolated from one another, since in humans each muscle fiber has just a single synapse on it. For that reason neuroscientists were able to study synaptic transmission here in great detail. We now use these results as a model for interpreting synaptic transmission in the brain.

Both impulse conduction and synaptic transmission rely on sophisticated ion channels like the one shown here. These integral membrane proteins have evolved the ability to sense small differences in electrical voltage or the presence of one or two molecules of a signaling chemical. They then alter their conformation and conduct ions across the membrane to change the transmembrane voltage. The last decades have brought enormous increases in our understanding of the structure and function of ion channels.

We will also study the huge family of G protein-coupled receptors that respond to hormones, neurotransmitters or external stimuli such as light or odors to trigger a cascade of chemical reactions in the cell.

In the second part of the course, we will emphasize the study of neuronal networks. Although it is convenient to study isolated neurons or small sets of neurons, an isolated neuron is as disadvantaged as an isolated person. Neurons, like people, can only realize their full potential in the context of others.

Each neuron in the brain is in incessant communication with many other neurons.

A single, large neuron in the brain of a fish is of special interest because of its huge size, which permits it to be identified in every fish. You can see dozens of tiny objects, like pollywogs, attached to the surface. This is a thin slice made by Dick Roth, formerly  in the Department of Biological Sciences. If we could see the tissue in 3 dimensions, this would be a furry tube. All of the fur is in fact synaptic input -- each one is an individual synaptic knob -- because hundreds of other neurons are competing in an attempt to make this neuron fire, that is, generate its own neural impulse, while another large set of neurons is trying to inhibit the neuron from firing. This cell is called a Mauthner neuron after the Austrian physician who first described it in 1859. Since this is a thin slice of brain tissue you can only see a portion of the cell body and one fat dendrite.

In this schematic, you can see the whole neuron, except its axon, which is so long that it runs the entire length of the spinal cord to the tail. This neuron is unusual among vertebrate neurons in that it is identifiable -- every fish has exactly one pair -- and it is also unusual in having a specific, known function. What happens when a neuron fires? For most neurons the answer is that we don't know. But the Mauthner neuron is a special neuron called a command neuron, which is has exceedingly powerful effects on behavior. When a Mauthner neuron fires the goldfish flips its tail and escapes.

This occurs because the axon of the Mauthner neuron runs the entire length of the spinal cord and fires motor neurons that flex the muscles on one side of the fish, so that the fish rapidly darts away from the stimulus.

The process of competition and cooperation among inputs to a neuron is called integration. Integration can be considered both as a physical process and as an information process -- and thus is the logical nexus of psychology and biology. Because of the importance of integration -- you can consider all of the lectures prior to this one as preparation for an understanding of integration. We will study neural integration by considering simple neural circuits which, like the molecular and physiological mechanisms of which they are composed, are common to both simpler animals and humans.

When discussing neural systems I will again stress the thesis that the secret to brain function lies in the intricate interconnections among nerve cells: the precisely patterned networks of neurons show special features, sometimes called emergent properties.

The study of neural systems is not nearly as advanced as the study of single neurons. It is also a huge topic that will necessarily require us to select among a wide set of possible topics.

For example, the study of vision can provide examples of how perceptual qualities, which we often consider to be paradigmatic examples of higher psychological or mental processes, can in selected cases be traced to the operations of rather simple neural circuits. Shown here is the painter's trick of creating the illusion of a bright window: the example is by Rembrandt, and was used by Thomas Albright in a Science commentary on studies of reciprocal connections among cortical neurons that are demonstrated to play role in such percepts. In this course, we will say relatively little about vision--not because it is unimportant, but because it is so important that it is extremely well covered in other classes at Stanford.

The eye-movement control system helps illustrate how complex neural circuits are critical to our behavior even when we are unaware of them. Four sets of muscles can direct the eyeball in any direction as a function of their relative tension. That tension is controlled by motor pathways which originate in the brain stem. The motor circuits, in turn, are influenced by sensory input from various sources, and by command pathways in the cortex.

Consider just one of the uses to which this system is put: your ability to read. If you observe the eyes of someone who is reading, they jerk across each line of type in 3 or 4 discrete jumps, called saccades, and then flick back to the margin like a typewriter carriage to begin again. This enormously precise and complex motor act is done so automatically and unconsciously that most people are entirely unaware of it.

In addition to being unaware of your eye movements when reading, most of us are also only dimly aware of the details of the words on the page. Especially if you are engrossed in a good novel, the succession of black and white patterns on the page is almost totally lost and you find yourself experiencing color, sound, and even emotions almost as though you were living them. These experiences become memories that can influence how we live.

As we saw earlier, the inherent ability of humans to read and write, present probably for at least 100,000 years but capitalized upon only much more recently, has led to a novel kind of evolution which is proceeding at an ever-accelerating i.e. and explosive, pace.

I conclude the commentary on the eye movement system by reminding you that our ability to feel emotion--to be made happy, sad, or frightened, can be induced by printed symbols on a page.

Is emotion beyond physiological study?

An emotion, such as delight, is not wholly intangible--it has some definable antecedents corollaries, and its physical basis and evolutionary significance can be studied, although it isn't easy.

In his famous work The Expression Of The Emotions In Animals And Man, Charles Darwin proposed that expressions can be innate, and can be caused by, and can in turn elicit, emotional states. We will look at some of the evidence for that idea, and for evidence of its limits.

Important topics that we will consider only briefly are learning and memory.

The Aplysia or sea hare has simple behavior but a spectacularly accessible nervous system because many of its neurons are giant and pigmented. For that reason, intensive studies of simple forms of learning have been carried out in this animal.

Studies of learning and memory emphasize the extent to which we can empower ourselves by learning new facts and new skills.  But we are not infinitely malleable--we can't learn to be fish or birds or elephants, and men can't learn to give birth.  Other, less obvious genetic influences are being studied with both new and old methods, even though such studies seem destined to be forever controversial.  For example, an international team of scientists recently reported that the heritability of general cognitive ability, as measured in a group of 240 pairs of twins who are all in their 80's, is 62%!  This figure is not different from that found at all other periods in life back to adolescence.  Thus, contrary to expectations, the genetic contribution to cognitive ability seems to be constant throughout life.  We will quickly review the vast topic of genes and behavior.

This brief introduction should allow you to decide if this course will be of interest or use to you.