November 5, 1996
Dr. Joseph LeDoux: Using Rats to Trace Routes of Fear

The realm of emotion and feeling is a treacherous one for science. Rage, lust, envy and shame churn in the human psyche. Yearning, disappointment and fear mingle with conscious thought, sway decisions and then recede like phantoms.

Writers, psychoanalysts and psychologists may try to sort out the interplay of cognition and desire, of thought and compulsion. But understanding the origin and architecture of human emotions in the brain is another matter altogether. What is the key to linking emotions to activity in the cells of the brain?

Rats -- better yet, frightened rats -- are the key, says Dr. Joseph LeDoux, a 46-year-old neuroscientist at New York University who pioneered the study of emotions as biological phenomena.

"You start with something you can study," LeDoux said in a recent interview. Like most animals, rats exhibit fear, an emotion that may help creatures escape from predators. In experiments over the last 15 years, LeDoux has traced fear inside the rat's brain -- from the first sounds of danger detected by the outer ear to inner brain circuits that cause the animal either to freeze or to run for its life.

Using this strategy, LeDoux has given researchers the first real glimpse into the neuroanatomy of an emotion. And though the work has been done in rats, Ledoux says the findings also apply to humans, providing insights into why it is so difficult to control emotions with rational, conscious thought.

One of the biggest surprises from LeDoux's work is that there may be no such thing as the limbic system -- a brain structure that has been supposed to underlie emotion and motivation. All students are taught about the limbic system, LeDoux said, "but in my opinion, it's no longer a valid concept."

Anatomists like LeDoux "are funny people," said Dr. Paul MacLean, the scientist who coined the term limbic system. "They think only about fear and rage," said MacLean, a senior researcher at the National Institute of Mental Health's Neuroscience Center in Washington. "They forget love, which more than anything else accounts for the development of the human race." The limbic system is still a valid concept, he said, adding that efforts to discard the idea were ill-founded.

But Dr. James McGaugh, a neurobiologist at the University of California in Irvine, has high praise for LeDoux. "Joe LeDoux is among a small number of people pushing the frontiers of how the brain provides a basis for our emotional responses," he said. "Emotions are not a dominant theme in neuroscience. He's been a modern pioneer."

Dr. Michael Gazzaniga, a neuroscientist at Dartmouth College in Hanover, N.H., said LeDoux had the courage to tackle a subject -- understanding the neuroanatomy of emotions in the brain -- that others thought was impossible to do. "Joe jumped in," Gazzaniga said, "and has unearthed some basic truths about the brain."

LeDoux may have ventured into a field that others avoided because he entered graduate school with virtually no training in biology. "I wasn't corrupted by too much knowledge," he said. "I was naive enough to think that emotions could be studied."

Raised in rural Louisiana, LeDoux said that he was not supposed to be a scientist. "My mother said she would pay for my college education if I studied business, so I did," he said. "I hated it. I didn't know what to do when I graduated from Louisiana State University, so I did more business school. I was interested in consumer issues, in Ralph Nader kinds of things, and wondered if the principles of the psychologist B.F. Skinner might be useful for understanding consumer behavior. So I wrote him a letter and he actually wrote back. He said it wouldn't be ethical."

LeDoux laughed. "That was it," he said. "I left business school with no regrets."

Looking for something new, LeDoux volunteered to work in a laboratory where he helped carry out experiments on rats and signed up for a course on the neural basis of learning and memory. He loved it, applied to 20 graduate schools and, with the help of his adviser, was accepted at just one, the State University of New York at Stony Brook.

Soon afterward, in 1974 and 1975, experiments carried out on so-called split brains attracted his attention. In people who had had the connection between the left and right brain hemispheres severed, the left side often did not know what the right side was doing. But emotional information seemed to be leaking across the hemispheres, suggesting a different sort of wiring than for language or movement.

"I thought why not study emotions?" LeDoux said.

He said that at the time cognitive scientists tended to confuse emotions and feelings. LeDoux says that emotions are hard-wired, biological functions of the nervous system that evolved to help animals survive in hostile environments and procreate. The emotional systems underlying fearful, sexual or feeding behaviors are pretty similar across species, though each emotion may have its own separate neural wiring.

Feelings, in LeDoux's scheme of things, are "red herrings," products of the conscious mind, labels we give to unconscious emotions. "What we really want to study is the brain system that generates emotions," LeDoux said, not the higher brain systems that read meaning into them. Because many researchers thought they first had to understand consciousness and feelings, he said, they were intimidated and stayed away from emotions.

In his new book, "The Emotional Brain" published this month by Simon & Schuster, LeDoux also describes how cognitive neuroscientists have tended to separate cognition and emotion as separate facets of mind. Since feelings are subjective, he said, they are very difficult to study objectively.

But that is not the case with emotions, LeDoux said. One can study how emotions are processed in the brain without reference to more complicated feelings. Having identified an emotion like fear, the questions are: What brain cells detect danger? How do they do it? What is the wiring diagram? What brain chemicals are used?

In 1977, LeDoux went to Cornell University Medical College to begin his rat studies and has continued them at New York University's Center for Neural Science since 1989. In the experiments, rats are exposed to a tone and mild electric shock at the same time. Later, at the sound of the tone by itself, they freeze, as if frightened. They have been conditioned to fear the noise.

While many researchers use this strategy to study memory and learning in animals, LeDoux has focused all his attention on emotions. "My approach was to let the natural flow of information through the brain be my guide," he said.

"I started where the sound stimulus enters the brain and tried to trace the pathways forward," not knowing in advance where they went, he said.

By using tracers, chemicals that stain neurons and thus show where they send their fibers, LeDoux found a direct pathway from the ear to a way station called the sensory thalamus that led directly to the amygdala, an almond-shaped structure in the forebrain. When this pathway was cut, rats could not be conditioned to fear a sound.

Most of the time, the amygdala is quiet, LeDoux said. But when it receives a strong stimulus, it sets sirens in motion. Hairs stand on end, the heart races and fight or flight hormones flood the body.

On closer examination, LeDoux found that the amygdala is designed to detect predators. For example, when rats are threatened, they emit very high frequency (20,000 to 30,000 cycles per second) screams. When another rat hears this scream, a signal goes from the auditory cortex, where sounds are processed, directly to the amygdala. In other words, says LeDoux, when these sound waves penetrate the rat brain, the amygdala is instantly activated even though it does not "know" the sound is coming from another rat.

The human brain is similarly wired, LeDoux said. A visual stimulus, perhaps the sight of a snake on a dirt path, will travel to the amygdala in a few thousandths of a second. The human amygdala contains cells that fire in response to expressions on faces and may also react to objects of fear.

But, LeDoux said, the amygdala is specialized for reacting to stimuli and triggering a physiological response, a process that he would describe as the "emotion" of fear. That is distinct from a conscious feeling of fear, LeDoux said. Feelings, he said, arise from a second, slower pathway that travels from the ear to the amygdala and then on to the higher cortex. There, the frightening stimulus is analyzed in detail, using information from many parts of the brain, and a message is sent back down to the amygdala.

If the message is a false alarm -- hey, it is a stick and not a snake -- the cortex will try to abort the amygdala's alarm signals. But the person will have felt a jolt because of the initial arousal of the amygdala.

This double pathway is very different from the limbic system that is taught to every biology student, LeDoux said. The limbic system is a hypothetical construct of pathways in the forebrain, which contains the hippocampus, amygdala and a few other tiny structures, that supposedly gets all sorts of sensory input from the external world -- sight, smell, hearing, touch and taste -- as well as from the viscera. When these sensations are integrated in the limbic system, emotional experiences occur.

The basic idea that there is a system for dealing with emotion that is divorced from cognition is a good one, LeDoux said. But when the fear circuit is actually traced, he said, the hippocampus and other "limbic" structures do not play much of a role. The amygdala alone sits at the center. Sensory information comes in and motor commands are sent out.

"This is how the brain does it," LeDoux said. Emotion and cognition are separate but interacting mental functions mediated by separate but interacting brain systems.

Such double wiring can create problems for people, LeDoux said. Neural connections from the cortex down to the amygdala are less well developed than are connections from the amygdala back up to the cortex. Thus, the amygdala exerts a greater influence on the cortex than vice versa. Once an emotion is turned on, it is difficult for the cortex to turn it off.

"This is why we have trouble controlling our emotions," LeDoux said. "They can really trip us up."

Fear is just one emotion, LeDoux said. The amygdala has 12 to 15 distinct regions and only two so far have been clearly implicated in fear. Other emotions might reside in the similar circuits but their anatomy has not been traced.

Another emotion well-suited to the rat brain tracing technique is sexual arousal. In humans, sexuality may be linked to love, which LeDoux would classify as a feeling rather than an emotion. While he is confident about the ability to understand sexual attraction's neural basis in rats and humans, he is not suggesting work on the neurobiology of love -- at least, not until the deeper puzzle of what gives rise to consciousness and feelings is solved.