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Editors Ronald Davis (Houston) Richard Morris (Edinburgh) Larry Squire (San Diego) Eric Kandel (New York) Carla Shatz (Berkeley) Charles Stevens (La Jolla)

Managing Editor Judy Cuddihy (Cold Spring Harbor)

Editorial Board

Per Anderson (Oslo) Martin Heisenberg (Wurzburg) Philippe Ascher (Paris) Susan Hockfleld (New Haven) Man D. Baddeley (Cambridge) Lawrence C. Katz (Durham) Carole A. Barnes (Tucson) Mary B. Kennedy (Pasadena) Timothy Bliss (London) Joseph Le Doux (New York) John Byrne (Houston) Hans-Peter Lipp (Zurich) Thomas J. Carew (New Haven) Stephen G. Lisberger (San Francisco) (Birmingham) Nick J. Mackintosh (Cambridge) John Conner (Nutley) Daniel Madison (Stanford) Thomas Curran (Nutley) Randolf Menzel (Berlin) Antonio Damasio (Iowa City) Mortimer Mishkin (Bethesda) Michael Davis (New Haven) Dennis D.M. O'Leary (LaJolla) Pietro De Camili (New Haven) Marcus Raichle (St. Louis) Yadin Dudai (Rehovot) Robert Rescorla (Philadelphia) Howard Eichenbaum (Stony Brook) Daniel Schacter (Cambridge) Yves Fr~gnac (Gif sur Yvette) James Schwartz (New York) Alison Goate (St. Louis) Wolf Singer (Frankfurt) Michael E. Greenberg (Boston) Richard Thompson (Los Angeles) Stephen Heinemann (La Jolla) Richard Tsien (Stanford)

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Copyright © 1994 by Cold Spring Harbor Institutional: U.S. $127; ILO.W. $137 sur- Copyright information: Authorization to Laboratory Press Introduction The introduction of a new journal LEARNING Fifth, and finally, the study of learning may & MEMORY by the Cold Spring Harbor Laboratory carry with it a special bonus. It may also provide Press reflects the conviction of the Editorial Board insights into one of the key mechanisms of neural that the biological study of learning is entering a development--the fine-tuning of synaptic connec- new and exciting phase. Although the study of tions. We have learned recently that the steps learning has traditionally been central to neu- whereby each axon is matched to specific postsyn- ropsychology, cognitive psychology, and to ethol- aptic target neurons occur through activity-depen- ogy, until quite recently this study was not a major dent mechanisms and that these mechanisms pro- concern for cell and molecular neurobiologists. duce the final point-to-point order required for the Within the last few years the situation has changed mature function of neural systems. Activity-depen- dramatically. The study of learning has suddenly dent selection seems to be required to fine-tune become a central and rapidly expanding field the connections but constitute the representation within biology. of many (perhaps all) sensory systems in the . Why has learning suddenly attracted a large Indeed, many of these connections can be modi- number of biologists? There are probably several fied by activity throughout the adult life of the reasons for this change. First, since the classic organism, illustrating a temporal continuity be- studies of the patient H.M., who had a bilateral tween development and learning. The specific removal of the medial temporal lobe, behavioral mechanisms for these activity-dependent changes understanding of the different forms of learning are not known. But the best candidates that have and memory has improved. so far emerged for these developmental processes, Second, neurobiologists have made remark- are those, like long-term potentiation, that utilize a able progress in analyzing, on the molecular level, Hebb-like mechanism similar to that employed for both the voltage-gated ion channels important for certain forms of learning and memory storage in impulse activity in nerve cells and the ligand-gated the adult animal. channels important for synaptic transmission. This For these several reasons we are launching success has not only increased the confidence of this journal, LEARNING & MEMORY, not passively neurobiologists but also has enhanced the concep- but proactively. We plan to do more than respond tual and methodological power that can now be to the perceived need for a journal that would brought to bear on the study of vesicle exocytosis welcome papers on learning, ranging from cogni- and . As a result, a number of tive studies in humans to molecular studies in in- molecular neurobiologists now are eager to tackle vertebrates. Rather, we are starting the journal more complex problems involving the modifiabil- with the idea of contributing actively to the intel- ity of systems of neurons. The most interesting of lectual growth of the field. We see this journal as these systems control behavior that can be modi- facilitating a new synthesis between the various fied by learning. areas concerned with the study of learning--be- Third, there is a gradual appreciation that tween cognitive studies of learning and memory, learning is central not only to cognitive psychol- computational and experimental studies of com- ogy but also to neural science. It is hard to think of plex systems, and cell and molecular biological making progress in either field without first under- studies of exocytosis and synaptic plasticity in sim- standing how behavior is generated, how it is mod- ple experimental systems. Indeed, it is our convic- ified by learning, and how that modification is tion that learning and memory represent the most stored by nerve cells as memory. Certainly, the promising domain of behavior for achieving a co- central aspect of any animal's behavior is the abil- herent unification of brain and mind. ity to learn from experience--an ability that We therefore eagerly welcome important pa- reaches its highest form in humans. Moreover, sev- pers in all areas of learning and memory. We seek eral of the most devastating neurological diseases to publish on topics ranging from human amnesia that afflict humankindmDown's syndrome, Hun- to gene expression, from systems neurobiological tington's disease, Alzheimer's diseaseminvolve studies of learning to synaptic plasticity in disas- loss of memory. sociated culture. We also welcome papers address- But interest is not usually sufficient to recruit ing the psychological processes of learning and serious commitments. The fourth reason that has memory, particularly where these are likely to captured the interest of many scientists was the have an impact upon neurological work. Our aim conviction that learning and memory are now ap- is to assure readability, high scientific standards, proachable with a wide variety of techniques rang- and good critical reviews of all areas important to ing from neuroimaging to cognitive psychology, the coherent study of learning and memory. from computational studies to studies of neural systems, from cell biology to genetically modified animals. The Editors Volume 1 January/February 1994 Number 1 Pages 1-82

INTRODUCTION ...... fmviii

Review

The Predictive Brain: Temporal Coincidence and Temporal Order in Synaptic Learning Mechanisms ...... 1 P. Read Montague and Terrence J. Sejnowski Research papers

Lesions of the Dorsal Hippocampal Formation Interfere with Background but Not Foreground Contextual Fear Conditioning ...... 34 Russell G. Phillips and Joseph E. LeDoux Hippocampal Formation Size in Normal Human Aging: A Correlate of Delayed Secondary Memory Performance ...... 45 James Golomb, Alan Kluger, Mony J. de Leon, Steven H. Ferris, Antonio Convit, Mary S. Mittelman, Jacob Cohen, Henry Rusinek, Susan De Santi, and Ajax E. George Potentiation of Dentate Synapses Initiated by Exploratory Learning in Rats: Dissociation from Brain Temperature, Motor Activity, and Arousal ...... 55 Edvard I. Moser, May-Britt Moser, and Per Andersen Recruitment of Long-lasting and Protein Kinase A-dependent Long-term Potentiation in the CA1 Region of Requires Repeated Tetanization ...... 74 Yan-You Huang and Eric R. Kandel

Cover Hippocampal formation size in normal human aging. A coronal Tl-weighted MRI in which the size of the hippocampal formation is determined by the number of pixels falling within the red boundaries. (See Golomb et al., p. 45, for details.)