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Modulating Memory

Joseph LeDoux

Memory and Emotion: The Making of Lasting Memories. James L. McGaugh. xii + 162 pp. Columbia University Press, 2003. $24.50.

In many ways, we are our memories. Or as the surrealist filmmaker Luis Buñuel put it, without memory we are nothing. Buñuel, it should be noted, came to this conclusion late in life, as his own capacity for memory was failing. We probably would all like our memory to work better, but most of us would settle for it simply not to deteriorate as we age. Fortunately, research on the topic is proceeding at a fast pace, and much is being learned about how memory normally functions and what causes it to falter. It seems likely that in the not-so-distant future we will have safe and effective ways of enhancing normal memory and also of treating, or maybe even preventing, at least some forms of memory loss.

In any successful area of research, it is easy for the past to be overshadowed by the excitement of the present. But in Memory and Emotion, James L. McGaugh gives a rich and insightful overview of modern memory research in the context of seminal discoveries of the past. Perhaps no one alive today is better suited to have written such a book. McGaugh, who is director of the Center for the Neurobiology of Learning and Memory and a professor of neurobiology and behavior at the University of California, Irvine, has himself investigated the biology of memory since the 1950s, and through his mentors he belongs to a scientific lineage in the study of memory that spans many decades. Although I too work in this field, I learned many things about its history from this concise, well-written book, which nonexperts will also enjoy. It relates many anecdotes that will help the lay reader appreciate the significance of experimental findings (many based on studies of rats) that shed light on how the human brain forms lasting memories.

One of the most important things we've learned about memory in recent years is that it is not a unitary brain function—rather, there are a variety of different brain systems that are capable of recording and storing information about life's experiences. Some of these make "memory" in the conventional sense of the term: That is, they preserve records of experience in such a way as to later allow conscious recollection of the past. These so-called explicit or declarative memories are products of the "medial temporal lobe memory system," which includes the hippocampus and related brain regions. Other systems, though, store information implicitly, or unconsciously. Sensory processing regions in the neocortex, for example, store information about certain sensory experiences, and the motor cortex and cerebellum allow learned movements to be stored. Also, a system involving the striatum stores habits—complex behavioral patterns that are learned and used in situations that routinely recur. McGaugh gives a cogent summary of how these and other systems store information.

Especially informative is McGaugh's summary of his main area of research, which has been in recent years not memory formation per se but the modulation of memory by chemicals released during the to-be-remembered experience. Modulation is to memory as spice is to food: Spice doesn't change nutritional value; it instead alters the way the food affects you. In other words, modulatory chemicals don't make memories; rather, they alter the properties of memories, affecting their persistence and possibly their accuracy.

McGaugh became interested in modulation in the 1950s when he discovered that certain drugs could boost memory in rats. It is important to keep in mind that improved performance on a test of memory may be the result of factors other than enhanced memory—for example, increased sensory acuity, alertness, motor activity or motivation. In humans with memory problems, performance is the most important thing from the point of view of the patient and loved ones—which might lead you to think that if a person with Alzheimer's disease copes better when taking a drug, it doesn't matter whether the drug is altering performance factors or memory. In fact, it does matter. For one thing, all drugs have side effects, and the more we understand about why a particular drug works or not, and what it is doing if it does work, the easier it will be to develop medicines that will do a better job. Also, science is about figuring things out. A scientist interested in memory can't settle for an effect on performance; scientists need to know how memory works.

In the 1960s, McGaugh pioneered an approach that helped rule out performance factors in the study of memory in laboratory settings. It was a simple but important trick: Instead of administering the drug before training an animal, he gave the drug immediately afterward. It could not have influenced performance during training, because it wasn't present. And he waited for the drug effect to wear off before evaluating memory, so that the drug could not affect performance during testing either. Thus its effects could be presumed to be on the consolidation of memory—the processes that occur in the minutes and hours after learning that are essential for the conversion of the initial experience into a lasting memory.

McGaugh has performed hundreds of experiments in which a drug is injected after training in order to characterize how memory is modulated, both by naturally occurring chemicals present in the brain and by drugs designed to improve memory. In some studies he has injected the drug systemically, so that it goes through the blood to all body parts, including the brain, but in others he has injected it into specific brain regions. One conclusion from this work is that the amygdala plays a key role in modulation, integrating chemicals during experience and then broadcasting a message to other regions of the brain (such as the hippocampus or striatum) that store specific kinds of memories.

The amygdala has long been implicated in emotional functions and is believed to be essential to the modulation of memory during emotional arousal, which explains why we remember emotionally significant events better than mundane ones. Given McGaugh's focus on the interrelation of emotion and memory, it may seem surprising to see little in his book about the amygdala's function in emotional memory. But McGaugh has long opposed the idea that the amygdala stores information about emotional experiences, believing instead that it simply modulates memory. I, and many others, agree with McGaugh that the amygdala modulates storage in the hippocampus, striatum and other brain regions. However, my own research supports the idea that the amygdala also stores information about emotional experiences—especially fearful ones, but perhaps others as well.

But this is not the place to argue about the amygdala. Memory and Emotion is about memory modulation, and on that topic it is superb. As McGaugh notes in his closing sentence, the final chapter about how memory works is not likely to be written soon. But thanks to him, the story of memory modulation is a well-told tale.

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