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A center at Columbia on mind, brain, and memory


THE CENTRAL PROBLEM in neuroscience is to understand the cognitive functions of the human mind: perception, action, emotion, language, learning, and memory. Techniques are now in place to tackle rigorously a set of cognitive problems relating to learning and memory. In the wake of the excitement generated by recent progress in molecular biology, there has been concern that these advances would lead to a separation of the molecular aspects of neural science (which deal with neuronal signaling) from the systems and cognitive aspects (which deal with behavior and higher mental functions). These problems, traditionally the province of psychologists and neurologists, are now being tackled with the tools of molecular biology. The time is right to apply molecular approaches directly to mental functions in animals and then to extend these findings to human cognition, using neuroimaging and other analytic approaches. We believe the Columbia faculty is appropriately positioned to provide national leadership in coordinating molecular biology, neural system studies, and cognitive psychology in a novel way, thereby founding a new discipline: the molecular biology of cognition.

To understand the brain, both as the organ of mental function and as a target for disease, we need to analyze animal and human behavior on the cellular and molecular levels. Among higher mental processes, those that relate to learning and memory seem particularly tractable. Our ability to remember events reflects not the operation of a single memory system but a combination of at least two strategies used by the brain to acquire information. One set of strategies, termed explicit memory, underlies memory for events and the circumstances of their occurrence; it requires conscious participation and involves the hippocampus and the temporal lobes of the cerebral cortex. The other set of strategies, implicit memory, encodes information about perceptual and motor skills, using non-cortical structures and requiring no conscious participation. Many learning tasks require both memory systems.

The Columbia neuroscience community has focused on three areas of memory research: the molecular analysis of the brain's mechanisms that underlie learning and memory in genetically modified mice (Professors Axel, Hen, Siegelbaum, and myself); the relation of developmental mechanisms to learning (Jessell, Kelley, Schwartz, Stern, and Macagno); and motor and perceptual learning in animals and humans, including clinical populations and model building of memory mechanisms (Cooper, Metcalfe, Ghez, Kupfermann, Qian, Mayeux, and Wexler). The investigators studying memory, which range from molecular biologists to cognitive psychologists and clinical investigators, are currently distributed through the University. We now propose to unite this faculty into an interdisciplinary Center on Mind, Brain, and Memory, representing the most extensive collaboration to date between the uptown and downtown divisions of the University. To achieve national leadership in the area, the center will require additional senior faculty to head this effort as well as six to eight junior faculty. Half these faculty additions will be located downtown and half uptown. The new faculty will be housed in approximately 10,000 square feet of space, again divided evenly between the two campuses. The cost for initiating the center is estimated to be about $20 million.

A particularly exciting new direction involves molecular approaches to memory storage in intact animals, using cognitive learning tasks analogous to those developed for human implicit and explicit learning, and parallel explorations of neural processing during these tasks in humans, using brain imaging. To examine activity in the human brain during thought and memory, these studies will involve a new imaging unit that combines positron emission tomography, xenon-133, single-photon-emission computed tomography, and magnetic resonance imaging. This center will also assume a coordinating and training role at the postgraduate, graduate, and undergraduate levels. In this way, the center will contribute to Columbia College's efforts to enhance undergraduate education in the biological sciences, particularly the biology of mind and brain.

The center proposes to ask a wide range of questions: How do individual genes contribute to different forms of learning and memory? What structural and biochemical alterations occur in specific nerve cells when an animal learns, and how does one establish a causal relation between cellular and behavioral changes? What is the relation between developmental plasticity and learning plasticity? What regions of the human brain are involved in implicit and explicit learning? What is the nature of parallel processing in learning? How is learning represented in a complex human motor or sensory system involving many parallel pathways? How do the two systems interact? How are implicit and explicit memory affected in normal aging? How are these processes affected by diseases known to impair cognition? To address these questions, the center will conduct four major research projects, plus a set of teaching programs.

Genetic mechanisms contributing to implicit and explicit memory: To bridge molecular studies of neuronal function to systems neural science and behavior, scientists in the center will focus on mouse genetics, an area in which Columbia has unique strengths. Genetically modified mice can provide information about the function of genes on molecular, cellular, and systems levels. Studies of transgenic animals also relate the functions of individual genes to behavior, learning, and behavioral abnormalities produced by disease.

Learning and developmental plasticity: To decipher changes in brain circuitry that create and maintain memories, we will need to understand how specific sets of nerve cells connect to each other. This effort at the center will focus on the genetic and activity-dependent mechanisms that produce changes in connections of neurons during development.

Parallel processing in neural systems for perception and action: Complex neural systems, such as those important for action or perception, work by means of parallel processing; they separate tasks into components, analyze them as separate streams, and recombine them as feats. Despite its importance, the role of parallel processing in implicit and explicit memory functions is poorly understood. This project will examine parallel processing in both simple experimental systems and in human beings.

Interaction of implicit and explicit memory to achieve perception and action: Implicit and explicit learning and memory can be functionally dissociated. However, under most circumstances, these two aspects of memory interact to produce smoothly orchestrated behavior: perception and action. This set of studies will explore interactions among memory systems using behavioral analysis and neuroimaging of cognitive functions in normal persons and patients.

The center's training functions will apply rigorous molecular-based and interdisciplinary methods to the range of aspects of learning and memory, including genetic approaches, animal behavior studies, and imaging of human memory storage. Advanced trainees will be molecular biologists, geneticists, psychologists, and clinicians from other disciplines who now are interested in receiving a broad-based molecular and cognitive neural science approach to development, behavior, and learning. At bimonthly seminars, members of this center will discuss their current research and examine interesting clinical cases. Investigators outside the university will be invited to present relevant novel findings. The center will also sponsor a weekly journal club to read critical papers in the field. Through this center we should be able to achieve a new level of behavioral analysis and teach trainees to think about psychological problems in a new way. Finally, we hope to develop two new courses: a graduate Introduction to Molecular Cognition and an introductory undergraduate Cognitive Neuroscience course connecting the humanities, concerned with human nature in its social context, to the molecular sciences and their concern with the neurobiology of mind.

ERIC KANDEL, M.D., is University Professor at Columbia in the Center for Neurobiology and Behavior and the Departments of Biochemistry and Molecular Biophysics, Physiology and Cell Biology, and Psychiatry.

ART CREDIT: University of California, Davis; adapted by Howard Roberts; mouse image courtesy of Eric Kandel.

A presidential view

The center has been a high priority for President Rupp, Provost Cole, Vice President for Health Sciences and Medical School Dean Herbert Pardes, and John Oldham, Director of the Psychiatric Institute.

President Rupp has summarized his views of the center in the following terms:

"First, the proposed center bridges the disciplinary gap between molecular and neural system studies of memory on the one hand and cognitive psychological studies of memory on the other. In doing so, the center addresses one of the central problems in neuroscience and one of the great challenges for biology: understanding the higher cognitive functions of the brain, including the human brain, on the molecular level.

"Second, the proposed center represents the most far-reaching effort at Columbia so far to engage the combined strengths of the faculties of Arts and Sciences on the Morningside Heights Campus and the Health Sciences on the campus of the Columbia-Presbyterian Medical Center. Kandel and Cooper, co-directors of the center, have drawn together the talents of leading scientists from departments all over the University. These departments range from psychology and psychiatry to biochemistry, genetics, neurobiology, and neurology. In so doing, the co-directors have created an innovative framework within which we hope to advance knowledge about higher mental functions as well as train people to think about behavior in a new way.

"Third, the center marks one step in a larger process of identifying selected areas of research for targeted investment. We will concentrate resources in these areas so as to develop distinctive strengths for which Columbia is known. The Center on Mind, Brain, and Memory clearly represents such an area and therefore has my strongest support."

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