Emotion, Memory The Author and the JOSEPH E. LEDOUX is in- terested in the neural founda- tion of memory and emotion. Brain He studies the anatomy, physiology and behavioral organization of these aspects of mental functioning. Le- The neural routes underlying Doux, the Henry and Lucy Moses Professor of Science at the formation of memories about New York University, is the recipient of two National In- primitive emotional experiences, stitute of Mental Health dis- tinctions: a Merit Award and such as fear, have been traced a Research Scientist Develop- ment Award. He has also re- ceived an Established Investi- by Joseph E. LeDoux gator Award from the Ameri- can Heart Association. espite millennia of preoccupation with every facet of human emotion, we are still far from explaining in a rigorous physiological sense this part of our mental experience. Neuroscientists have, in modern times, been especially concerned with the neural basis of such cognitive pro- Dcesses as perception and memory. They have for the most part ignored the brain’s role in emotion. Yet in recent years, interest in this mysterious mental terrain has surged. Catalyzed by breakthroughs in understanding the neural basis of cognition and by an increasingly sophisticated knowledge of the anatomical organization and physiology of the brain, investigators have begun to tackle the problem of emotion. One quite rewarding area of research has been the inquiry into the relation between memory and emotion. Much of this examination has involved studies of one particu- lar emotion—fear—and the manner in which specific events or stimuli come, through individual learning experiences, to evoke this state. Scientists, myself included, have Memories of disturbing been able to determine the way in which the brain shapes how we form memories experiences form deep within about this basic, but significant, emotional event. We call this process “emotional our brains. memory.” By uncovering the neural pathways through which a situation causes a creature to learn about fear, we hope to elucidate the general mechanisms of this form of memo- ry. Because many human mental disorders—including anxiety, phobia, post-traumat- ic stress syndrome and panic attack—involve malfunctions in the brain’s ability to control fear, studies of the neural basis of this emotion may help us further understand and treat these disturbances. Most of our knowledge about how the brain links memory and emotion has been gleaned through the study of so-called classical fear conditioning. In this process the subject, usually a rat, hears a noise or sees a flashing light that is paired with a brief, mild electric shock to its feet. After a few such experiences, the rat responds automat- ically to the sound or light, even in the absence of the shock. Its reactions are typical to any threatening situation: the animal freezes, its blood pressure and heart rate in- SPL/Photo Researchers, Inc. Inc. SPL/Photo Researchers, crease, and it startles easily. In the language of such experiments, the noise or flash is a conditioned stimulus, the foot shock is an unconditioned stimulus, and the rat’s reac- tion is a conditioned response, which consists of readily measured behavioral and MEHAM KULYK MEHAM KULYK physiological changes. 68 Mysteries of the Mind Reprinted from the June 1994 issue Copyright 1997 Scientific American, Inc. Conditioning of this kind happens quickly in rats—indeed, it takes place as rapidly as it does in humans. A single pairing of the shock to the sound or sight can bring on the conditioned ef- fect. Once established, the fearful reac- tion is relatively permanent. If the noise or light is administered many times with- out an accompanying electric shock, the rat’s response diminishes. This change is called extinction. But considerable evi- dence suggests that this behavioral al- teration is the result of the brain’s con- trolling the fear response rather than the elimination of the emotional memo- ry. For example, an apparently extin- guished fear response can recover spon- taneously or can be reinstated by an ir- relevant stressful experience. Similarly, stress can cause the reappearance of phobias in people who have been suc- AUDITORY CORTEX HIPPOCAMPUS O OSTI T OBER R AUDITORY THALAMUS HIPPOCAMPUS AMYGDALA ANATOMY OF EMOTION includes several regions of the brain. Shown here in the rat (above), parts of the amygdala, the thalamus and the cortex interact to create memories about fearful experiences opic associated, in this case, with sound. Re- osc cent work has located precise areas where icr fear is learned and remembered: certain APL M parts of the thalamus (light pink at top right) communicate with areas in the amygdala (light yellow at bottom right) W LEONARD that process the fear-causing sound stim- uli. Because these neural mechanisms are HS BY ANDRE thought to be similar in humans, the study AP OGR of emotional memory in rodents may illu- T HO minate aspects of fear disorders in people. P Emotion, Memory and the Brain Mysteries of the Mind 69 Copyright 1997 Scientific American, Inc. SOUND ELECTRICITY 20 10 20 10 20 10 ) ORPOLE IAN W 8 8 8 15 15 15 6 6 6 10 10 10 MILLIMETERS OF MERCURY 4 4 4 BLOOD PRESSURE BLOOD PRESSURE CESSATION OF MOVEMENT 5 5 CESSATION OF MOVEMENT 5 2 2 2 BLOOD PRESSURE ( 0 CESSATION OF MOVEMENT (CUMULATIVE SECONDS) 0 0 0 0 0 0 10 0 10 0 10 0 10 0 10 0 10 TIME (SECONDS) CLASSICAL FEAR CONDITIONING can be brought about shock (center). After several such pairings, the rat’s blood pres- by pairing a sound and a mild electric shock to the foot of a rat. sure rises at the same time that the animal holds still for an ex- In one set of experiments, the rat hears a sound (left), which has tended period when it hears the sound. The rat has been fear- little effect on the animal’s blood pressure or patterns of move- conditioned (right): sound alone achieves the same physiological ment. Next, the rat hears the same sound, coupled with a foot changes as did sound and shock together. cessfully treated. This resurrection dem- or humans, for that matter—encounter because the shock modifies the way in onstrates that the emotional memory un- in their daily lives. The novelty and ir- which neurons in certain important re- derlying the phobia was rendered dor- relevance of these lights and sounds help gions of the brain interpret the sound mant rather than erased by treatment. to ensure that the animals have not al- stimulus. These critical neurons are ready developed strong emotional reac- thought to be located in the neural path- Fear and Emotional Memory tions to them. So researchers are clearly way through which the sound elicits the observing learning and memory at conditioned response. ear conditioning has proved an ide- work. At the same time, such cues do During the past 10 years, researchers Fal starting point for studies of emo- not require complicated cognitive pro- in my laboratory, as well as in others, tional memory for several reasons. First, cessing from the brain. Consequently, have identified major components of this it occurs in nearly every animal group the stimuli permit us to study emotional system. Our study began at Cornell Uni- in which it has been examined: fruit mechanisms relatively directly. Finally, versity Medical College, where I worked flies, snails, birds, lizards, fish, rabbits, our extensive knowledge of the neural several years ago, when my colleagues rats, monkeys and people. Although no pathways involved in processing acous- and I asked a simple question: Is the au- one claims that the mechanisms are pre- tic and visual information serves as an ditory cortex required for auditory fear cisely the same in all these creatures, it excellent starting point for examining conditioning? seems clear from studies to date that the the neurological foundations of fear In the auditory pathway, as in other pathways are very similar in mammals elicited by such stimuli. sensory systems, the cortex is the high- and possibly in all vertebrates. We there- My work has focused on the cerebral est level of processing; it is the culmina- fore are confident in believing that many roots of learning fear, specifically fear tion of a sequence of neural steps that of the findings in animals apply to hu- that has been induced in the rat by as- starts with the peripheral sensory recep- mans. In addition, the kinds of stimuli sociating sounds with foot shock. As do tors, located, in this case, in the ear. If most commonly used in this type of most other investigators in the field, I lesions in (or surgical removal of) parts conditioning are not signals that rats— assume that fear conditioning occurs of the auditory cortex interfered with 70 Mysteries of the Mind Emotion, Memory and the Brain Copyright 1997 Scientific American, Inc. fear conditioning, we could conclude J. Reis and I looked again and found work suggested that the central nucleus O OSTI T that the region is indeed necessary for that, in fact, cells in some regions of the was a crucial part of the system through OBER R this activity. We could also deduce that auditory thalamus also give rise to fibers which autonomic conditioned respons- the next step in the conditioning path- that reach several subcortical locations. es are expressed. way would be an output from the audi- Could these neural projections be the In a similar vein, we found that lesions tory cortex. But our lesion experiments connections through which the stimu- of this nucleus prevented a rat’s blood in rats confirmed what a series of other lus elicits the response we identify with pressure from rising and limited its abil- studies had already suggested: the audi- fear? We tested this hypothesis by mak- ity to freeze in the presence of a fear- tory cortex is not needed in order to ing lesions in each one of the subcorti- causing stimulus.