The Behavior of the Laboratory Rat: A Handbook with Tests

The Behavior of the Laboratory Rat

THE BEHAVIOR OF THE LABORATORY RAT A Handbook with Tests

Edited by IAN Q. WHISHAW BRYAN KOLB Department of Psychology and Neuroscience Canadian Centre for Behavioural Neuroscience

OXFORD UNIVERSITY PRESS 2005

OXFORD UNIVERSITY PRESS

Oxford New York Auckland Bangkok Buenos Aires Cape Town Chennai Dar es Salaam Delhi Hong Kong Istanbul Karachi Kolkata Kuala Lumpur Madrid Melbourne Mexico City Mumbai Nairobi Sao Paulo Shanghai Taipei Tokyo Toronto

Copyright © 2005 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York, 10016 www.oup.com Oxford is a registered trademark of Oxford University Press All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Oxford University Press Library of Congress Cataloging-in-Publication Data Whishaw, Ian Q., 1939The behavior of the laboratory rat : a handbook with tests / edited by Ian Q. Whishaw, Bryan Kolb. p. cm. ISBN 0-19-516285-4 1. Rats—Behavior. 2. Rats as laboratory animals. I. Kolb, Bryan, 1947- II. Tide. QL737.R666W52 2004 616'.02733—dc22 2004041514

987654321 Printed in the United States of America on acid-free paper

To Samuel Anthony (Tony) Barnett (1915-2003) Behavioral neuroscientists know S.A. Barnett best for his book The Rat: A Study in Behavior, first published in 1963. He was the author of over 150 papers (the last of which is the second chapter of this volume) and nine books. He was a graduate of Oxford University in Zoology. He advised the British Government on plague during WWII and was the Chair of Zoology in Glasgow from 1971 to 1983. Tony was an enthusiastic broadcaster, contributing for years to the BBC series Occam's Razor.

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Preface

The principal function of the nervous system is to produce behavior. Thus, the ultimate goal of most behavioral work with laboratory animals in neuroscience is to understand how molecular events in the nervous system come to produce behavior and, as a corollary, how changes in molecular events produce differences in behavior. Understanding these issues offers hope for understanding the nature of the human mind, which some may argue is the fundamental question in neuroscience. But perhaps even more important is that understanding brain-behavior relationships offers a way to find treatments for dysfunctions of behavior, whether they are in the province of neurology or psychiatry. Advances in molecular and cellular neuroscience have been dramatic over the past two decades, but most of these advances have been independent of an understanding of how they relate to behavior. This is changing. Neuroscientists oriented toward molecular research are increasingly looking to the ultimate function of the phenomenon that they have been studying— behavior. For the majority of behavioral studies, this means studying the behavior of the laboratory rat. This book has three objectives. Our first objective is to present an introduction of rat behavior to neuroscience students. In choosing the rat as the subject species, we made the assumption that this species will remain, as it has in the past, the primary subject used the laboratory investigations of behavior. Our second objective is to describe the organization and complexity of rat behavior. The major theme emerging from many lines of research on rat behavior is that understanding the rules of behavioral organization will be

central in understanding the structural basis of behavior. Our third objective is to update, as much as is possible, previous compendiums of rat behavior. Behavioral neuroscience continues to be a diverse field of research in which there remain many competing experimental methods and hypotheses, and we believe that collectively, the chapters of this volume reflect that diversity. As we have noted, advances in the field of neuroscience have kindled an interest in behavior by researchers in many of its subdisciplines. For many of these researchers, behavior may previously have seemed unrelated to their studies and of little direct interest. Many researchers with primary training in diverse fields such as genetics or biochemistry are now looking at brain-behavior questions for the first time and, like all fields, the literature can be bewildering to the novice. We therefore asked the authors of the chapters of this book to imagine that students from another discipline were coming to them with questions related to how they could incorporate behavior into their research programs. For example, we asked them to imagine a student coming from such areas as medicine, chemistry, or genetics who had no special training in behavior but now saw behavior as relevant and necessary to research questions in which they were interested. The challenge we presented was, "Could they summarize their field of expertise so that the novice student would gain an understanding of the questions, methods, and potential findings in that line of research?" We also asked them to make their summary brief, to emphasize methodology, and to minimize as much as possible literature reviews. Our expectation is that a novice stuvii

viii

dent would read their chapter as a first introduction to the study of rat behavior. This introduction would then guide the student as he or her gained further expertise in the practical application of that information and in study of the larger body of literature. In our view, the problem that we posed is not fictive. During the past few years, we received large numbers of telephone calls, emails, and queries regarding behavior from people with diverse backgrounds in neuroscience. We have also been asked to speak at meetings about behavior to scientists who we could not have imagined would have been interested in behavior or in the research that we do. The tone of this interest is best represented by the comments of an acquaintance, a molecular biologist, who stated: "I could not have imagined that this psycho mumbo-jumbo was going to be important, but now I see it as the only game in town." We realize that in answer to such interest, it is simply not good enough to say, "We could look at that for you," or "Perhaps you should collaborate with an expert on that behavior." Rather, it is likely that behavioral methods will become a part of many lines of research, so the challenge for behaviorists is to make their science accessible to other investigators. Indeed, we have encountered the problem in reverse as we have added more molecular techniques to our behavioral studies. Accordingly, we asked the authors of the chapters in this book to make their research accessible to new students of behavior. Of course, this book is about rat behavior. The rat, Rattus norvegicus, was the first species to be domesticated for the purpose of scientific research. In the 100 years since the rat was first introduced to the laboratory, it has generated an incredibly large body of literature. It has been the primary subject with which psychological theories have been tested; it has been the primary subject for the study of behavioral pharmacology; and it has been the primary subject for the investigation of brain chemistry, anatomy, and physiology. One reason for the popularity of the rat is that

PREFACE

it is a behavioral generalist. Rats are found in virtually every ecological niche on earth, and they have proved to be adaptable and successful in all of them. For the purposes of answering behavioral questions, we assert that as a behavioral generalist, the rat will remain the primary species for continued investigations into the organization of brain and behavior and the structural basis of behavior. In being a generalist, the rat is very much like the human, a species with which it is commensal. It is likely that the genes, neural structure, and behavior of generalists have properties that are similar. This is why the rat continues to be the primary model used to study a wide range of questions related to human behavior and health. With the development of genetic engineering, a line of inquiry that uses the mouse as the prime vertebrate model, we should address the question of whether the mouse might not have been a better species about which to compile a behavioral book. The laboratory mouse is the laboratory rat's closest domestic relative, but we do not think that the two species are so similar that one can be substituted for the other. This is especially so with respect to behavior. Both species have been used for behavioral research for approximately 100 years, and each has apparently found its laboratory niche. There is little doubt that for many questions related to motor functions, regulatory functions, and especially cognitive functions, the rat has been the species of choice. We think that it will continue to be so. In contrast, mice will likely continue to be the subject of choice in genetic studies in neuroscience, and presumably the study of many behavior genetic questions will retain the mouse as the primary laboratory subject. However, the behavioral study of the mouse in genetics is fundamentally different from the primary questions addressed in behavioral studies in the rat and must be the subject of a separate volume. Two excellent, and still relevant, books have been previously devoted to rat behavior.

Preface

Norman L. Munn's 1950 "Handbook of Psychological Research on the Rat: An Introduction to Animal Psychology" is directed to many of the same questions as is the present book. It describes general activity, unlearned behavior, sensory processes, learning, social behavior, and rat models of neuropsychiatric diseases. It also emphasizes methods of study. S. A. Barnett's 1963 book, "The Rat: A Study in Behavior," covers much of the same ground but with more emphasis on the ethogram, or profile of behavior, of the wild rat. In what way is the present book different from these predecessors? We think that the primary advancement in understanding rat behavior is the emergence of understanding how rat behavior is organized. For example, rat grooming, play and aggression, exploration, cognition, and other activities are organized with both fixed and open syntax. The understanding of this organization provides new avenues for the investigation of genetic, neural, and hormonal regulation of behavior. This organization has also led to the development of computer-based behavioral analysis systems that aid in using behavior as an assay for other scientific manipulations. Although this book consists of 43 chapters on different aspects of rat behavior, and thus is

ix

comprehensive, it is not exhaustive. Our major difficulty in editing the book was in insisting that authors substantially shorten their chapters to make the book manageable as a single volume. Indeed, we could have doubled the number of chapters without covering every aspect of rat behavior, but we believe that the selection of chapters presented here provide more than adequate grist for an introduction to the study of the rat in behavioral brain research. We express a special thanks to all of the authors who generously contributed time to write a chapter for this book. We also express our thanks to Fiona Stevens of Oxford University Press, who approached us and persuaded us to compile this handbook and gave us the liberty of selecting a structure of our own choosing. Lethbridge, Alberta, Canada.

I. Q. W. B. K.

SUGGESTED READINGS Barnett SA (1963) The rat: a study in behavior. Chicago and London: The university of Chicago Press. Munn NL (1950) Handbook of psychological research on the rat: an introduction to animal psychology. Boston: The Riverside Press Cambridge.

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Contents

Contributors, xiii

13. Grooming, 141 J. Wayne Aldridge

Part I

14. Locomotion, 150 Gillian Muir

Natural History

1. Evolution, 3 Andrew N. Iwaniuk 2. Ecology, 15 S. Anthony Barnett 3. Strains, 25 Lauren Gerard Koch and Steven L Britton 4. Individual Differences, 37 Guy Mittleman Part II

Sensory Systems

5. Vision, 49 Glen T. Prusky and Robert M. Douglas

15. Prehension, 162 Ian Q. Whishaw 16. Locomotor and Exploratory Behavior, 171 Ilan Golani, Yoav Benjamini, Anna Dvorkin, Dina Lipkind, and Neri Kafkafi 17. Circadian Rhythms, 183 Michael C. Antle and Ralph E. Mistlberger Part IV

Regulatory Systems

18. Eating, 197 Peter G. Clifton 19. Drinking, 207 Neil E. Rowland

6. Somatosensation, 60 Linda Hermer-Vazquez, Raymond Hermer-Vazquez, and John K. Chapin

20. Foraging, 217 Ian Q. Whishaw

7. Pain, 69 Daniel Le Bars and Samuel W. Cadden

21. Thermoregulation, 226 Evelyn Satinoff

8. Vibrissae, 81 Richard H. Dyck

22. Stress, 236 Jaap M. Koolhaas, Sietse F. de Boer, and Bauke Buwalda

9. Olfaction, 90 Burton Slotnick, Heather Schellinck, and Richard Brown

23. Immune System, 245 Hymie Anisman and Alexander W. Kusnecov

10. Taste, 105 Alan C. Spector

Part V

Part III

24. Prenatal Behavior, 257 Scott R. Robinson and Michele R. Brumley

Motor Systems

Development

11. Posture, 121 Sergio M. Pellis and Vivien C. Pellis

25. Infancy, 266 Jeffrey R. Alberts

12. Orienting and Placing, 129 Tim Schallert and Martin T. Woodlee

26. Adolescence, 278 Russell W. Brown

xi

CONTENTS

xii

27. Maternal Behavior, 287 Stephanie L. Rees, Vedran Lovic, and Alison S. Fleming

Part VII

Cognition

36. Object Recognition, 383 Dave G. Mumby

28. Play and Fighting, 298 Sergio M. Pellis and Vivien C. Pellis

37. Piloting, 392 Etienne Save and Bruno Poucet

29. Sex, 307 William J. Jenkins and Jill B. Becker

38. Dead Reckoning, 401 Douglas G. Wallace and Ian Q. Whishaw

30. Environment, 321 Robbin L. Gibb

39. Fear, 410 Matthew R. Tinsley and Michael S. Fanselow

Part VI

40. Cognitive Processes, 422 Robert J. Sutherland

Defense and Social Behavior

31. Antipredator Defense, 335 D. Caroline Blanchard and Robert J. Blanchard

41. Incentive Behavior, 436 Bernard W. Balleine

32. Aggressive, Defensive, and Submissive Behavior, 344 Klaus A. Miczek and Sietse F. de Boer

Part VIII

33. Defensive Burying, 353 Dallas Treit and John J. P. Pinel 34. Social Learning, 363 Bennett G. Galef, Jr. 35. Vocalization, 371 Greta Sokoloff and Mark S. Blumberg

Models and Tests

42. Neurological Models, 449 Bryan Kolb 43. Psychiatric Models, 462 Henry Szechtman and David Eilam 44. Neuropsychological Tests, 475 Gerlinde A. Metz, Bryan Kolb, and Ian Q.Whishaw Index, 499

Contributors

JEFFREY R. ALBERTS

ROBERT J. BLANCHARD

Department of Psychology Indiana University Bloomington, Indiana

Department of Neurobiology University of Hawaii Honolulu, Hawaii

J. WAYNE ALDRIDGE

MARK S. BLUMBERG

Departments of Neurology and Psychology University of Michigan Ann Arbor, Michigan

Department of Psychology Indiana University Bloomington, Indiana

HYMIE ANISMAN Institute of Neurosciences Carelton University Ottawa, Ontario, Canada

MICHAEL C. ANTLE Department of Psychology Columbia University New York, New York

BERNARD W. BALLEINE Department of Psychology and the Brain Research Institute University of California, Los Angeles Los Angeles, California

S. ANTHONY BARNETT* Aranda, Australia

JILL B. BECKER Department of Psychology Reproductive Sciences Program and Neurosciences Program University of Michigan Ann Arbor, Michigan

YOAV BENJAMINI Department of Zoology Tel Aviv University Tel Aviv, Israel

D. CAROLINE BLANCHARD Department of Neurobiology University of Hawaii Honolulu, Hawaii Deceased.

STEVE L. BRITTON Functional Genomics Laboratory Medical College of Ohio Toledo, Ohio

RICHARD BROWN Department of Psychology Dalhousie University Halifax, Nova Scotia, Canada

RUSSELL W. BROWN Department of Psychology East Tennessee State University Johnson City, Tennessee

MICHELE R. BRUMLEY Department of Psychology University of Iowa Iowa City, IA

BAUKE BUWALDA Department of Animal Physiology University of Groningen Haren, The Netherlands

SAMUEL W. CADDEN The Dental School University of Dundee Dundee, Scotland

JOHN K. CHAPIN Department of Physiology and Pharmacology SUNY Downstate Medical Center Brooklyn, New York

xiii

CONTRIBUTORS

xiv

PETER G. CLIFTON

ILAN GOLANI

Department of Psychology University of Sussex Brighton, United Kingdom

Department of Zoology George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv, Israel

SIETSE F. DE BOER Department of Animal Physiology University of Groningen Haren, The Netherlands

ROBERT M. DOUGLAS

LINDA HERMER-VAZQUEZ Department of Physiology and Pharmacology SUNY Downstate Medical Center Brooklyn, New York

RAYMOND HERMER-VAZQUEZ

Centre for Macular Research Department of Ophthalmology and Visual Sciences University of British Columbia Vancouver, British Columbia, Canada

Department of Physiology and Pharmacology SUNY Downstate Medical Center Brooklyn, New York

ANNA DVORKIN

ANDREW N. IWANIUK

Department of Zoology George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv, Israel

WILLIAM J. JENKINS

RICHARD H. DYCK Department of Psychology Department of Cell Biology and Anatomy University of Calgary Calgary, Alberta, Canada DAVID ElLAM Department of Zoology Tel Aviv University Tel Aviv, Israel

MICHAEL S. FANSELOW Department of Psychology University of California, Los Angeles Los Angeles, California

ALISON S. FLEMING

Department of Psychology University of Alberta Edmonton, Alberta, Canada Department of Psychology Reproductive Sciences Program and Neurosciences Program University of Michigan Ann Arbor, Michigan

NERI KAFKAFI Maryland Psychiatry Research Center University of Maryland College Park, Maryland

LAUREN GERARD KOCH Functional Genomics Laboratory Medical College of Ohio Toledo, Ohio

BRYAN KOLB

Department of Psychology University of Toronto at Missassauga Missassauga, Ontario, Canada

Canadian Centre for Behavioural Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

BENNETT G. GALEF, JR.

JAAP M. KOOLHAAS

Department of Psychology McMaster University Hamilton, Ontario, Canada

Department of Animal Physiology University of Groningen Haren, The Netherlands

ROBBIN L. GlBB Canadian Centre for Behavioural Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

ALEXANDER W. KUSNECOV Department of Psychology Biopsychology and Behavioral Neuroscience Program Rutgers, The State University of New Jersey Piscataway, New Jersey

XV

Contributors

DANIEL LE BARS

VIVIEN C. PELLIS

Institut National de la Sante et de la Recherche Medicale (INSERM) Paris, France

Canadian Centre for Behavioral Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

DlNA LlPKIND Department of Zoology George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv, Israel

JOHN J.P. PlNEL Department of Psychology University of British Columbia Vancouver, British Columbia, Canada

VEDRAN Lovic

BRUNO POUCET

Department of Psychology University of Toronto at Missassauga Missassauga, Ontario, Canada

GERLINDE A. METZ Canadian Centre for Behavioral Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

KLAUS A. MICZEK Department of Psychology, Psychiatry, Pharmacology, and Neuroscience Tufts University Medford, Massachusetts

RALPH E. MISTLBERGER Department of Psychology Simon Fraser University Burnaby, British Columbia, Canada GUY MlTTLEMAN Psychology Department University of Memphis Memphis, Tennessee

GILLIAN MUIR Biomedical Sciences Western College of Veterinary Medicine University of Saskatchewan Saskatoon, Saskatchewan, Canada

Laboratoire de Neurobiology de la Cognition, UMR 6155 CNRS—Universite Aix-Marseille I Marseille, France

GLEN T. PRUSKY Canadian Centre for Behavioural Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

STEPHANIE L. REES Department of Psychology University of Toronto at Missassauga Missassauga, Ontario, Canada

SCOTT R. ROBINSON Department of Psychology University of Iowa Iowa City, Iowa

NEIL E. ROWLAND Department of Psychology University of Florida Gainesville, Florida

EVELYN SATINOFF Department of Psychology University of Delaware Newark, Delaware

DAVE G. MUMBY

ETIENNE SAVE

Department of Psychology Concordia University Montreal, Quebec, Canada

Laboratoire de Neurobiology de la Cognition, UMR 6155 CNRS—Universite Aix-Marseille I Marseille, France

SERGIO M. PELLIS Canadian Centre for Behavioral Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

TlM SCHALLERT Department of Psychology University of Texas at Austin Austin, Texas

CONTRIBUTORS

xvi

HEATHER SCHELLINCK

MATTHEW R. TINSLEY

Department of Psychology Dalhousie University Halifax, Nova Scotia, Canada

Department of Psychology University of California, Los Angeles Los Angeles, California

BURTON SLOTNICK Department of Psychology University of South Florida Tampa, Florida

GRETA SOKOLOFF Department of Psychology Indiana University Bloomington, Indiana

ALAN C. SPECTOR Department of Psychology University of Florida Gainesville, Florida

ROBERT J. SUTHERLAND Canadian Centre for Behavioural Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

DALLAS TREIT Department of Psychology University of Alberta Edmonton, Alberta, Canada

DOUGLAS G. WALLACE Canadian Centre for Behavioural Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

IAN Q. WHISHAW Canadian Centre for Behavioural Neuroscience Department of Psychology and Neuroscience University of Lethbridge Lethbridge, Alberta, Canada

HENRY SZECHTMAN Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton, Ontario, Canada

MARTIN T. WOODLEE Department of Psychology University of Texas at Austin Austin, Texas

Natural History

I

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1

Evolution ANDREW N. IWANIUK

ON THE ORIGIN OF Rattus norvegicus The Norway, or "laboratory," rat (Rattus norvegicus) has been used in behavioral, neural, physiological, and other forms of research for more than a century. The evolutionary history of this species is often dismissed as unimportant in psychological and biomedical research because the aim is not to understand evolutionary biology but rather to use the rat as a model system to investigate a specific aspect of organismal biology. It is not our intention to critique these experiments because they are integral to our understanding of animal behavior, anatomy, molecular biology, and physiology. It is, however, important to acknowledge that the rat did not evolve in a vacuum and that the morphological, physiological, and behavioral changes imposed by "domestication" are still a result of the evolutionary process. This chapter addresses the evolution of the laboratory rat from the origins of rodents in general to the speciation of the genus Rattus. This is not meant to be a complete review of all the taxonomy and phylogenetic history of Rattus and higher-level taxonomic ranks, because discussions of this are provided elsewhere (Carleton and Musser, 1984; Luckett and Hartenberger, 1985; Musser and Carleton, 1993; Nowak, 1999). Instead, I provide a summary of the evolutionary events that led to R. norvegicus. Because palaeontology, taxonomy, and phylogenetics are intimately related to one another, this chapter is organized

in terms of the taxonomy of R. norvegicus (Table 1-1). Evolutionary relationships and palaeontological history are discussed with reference to other groups of the same taxonomic rank. For example, the order Rodentia is placed in the context of other mammalian orders. By summarizing the evolutionary history of R. norvegicus, we aim to provide a basic understanding of how the species has evolved that may be instructive in interpreting the results of behavioral experimentation and/or comparative analyses.

ORDER RODENTIA To understand the evolution of R. norvegicus, it is necessary to begin with the history of the rodents in general and their relationship to other mammalian taxa. The order Rodentia is the most abundant of all of the mammalian orders, numbering close to 2000 species. Rodents are found on every continent, except Antarctica, and account for almost half of all placental mammals. They are readily distinguishable from other mammals by an array of morphological features (Luckett and Hartenberger, 1993, 1985), the most prominent of which is their distinctive dental morphology. Rodent incisors are large, unrooted, and persistently growing teeth with enamel only on the upper surface that maintains a beveled cutting edge. The surface morphology of the molars is also distinctive, and the jaw structure exhibits adaptations that allow considerable movement during grinding (Hand, 1984). 3

NATURAL HISTORY

4

Table 1-1. Taxonomy of the Genus Rattus Class Mammalia Order Rodentia Superfamily Muroidea Family Muridae Genus Rattus Species adustus argentiventer* bontanus colletti enganus exulans* foramineus giluwensis hoffinanni jobiensis korinchi losea* lutreolus marmosurus mollicomulus mordax nativitatis^ norvegicus* osgoodi pelurus ranjiniae sanila simalurensis steini tanezumi timorensis tunneyi villosissimus

annandalei baiuensis burrus elaphinus everetti feliceus fusdpes hainaldi hoogerwerfi koopmani leucopus lugens mackaritf mindorensis montanus morotaiensis nitidus* novaeguineae palmarum praetor rattus* sikkimensis sordidus stoicus tawitawiensis tiomanicus* turkestanicus xanthurus

Note: The taxonomy is taken from Guy and Musser (1993). *Commensal species. fSpecies that recently became extinct.

Despite some broad similarities in morphology, rodents are a morphologically and behaviorally diverse order. They span a range of locomotor behaviors that include gliding, climbing, swimming, underground digging, hopping, and running. Not only do rodents exhibit this range of locomotor behaviors; in most instances, they have evolved independently many times. For example, subterranean locomotion has evolved at least three times (Muroidea, Geomyoidea, Bathyergoidea). Similarly, there is a broad range of social systems from uniparental monogamy/polygamy to

complex, multimale/multifemale societies have also evolved independently many times. This behavioral diversity belies the fact that the rodents form a monophyletic group. That is, all rodents share a common ancestry that is not shared with nonrodent species. Although the issue of rodent monophyly was questioned by molecular studies of the guinea pig (Cavia porcdlus} (Graur et al., 1991; D'Erchia et al., 1996), more recent studies agree that rodents are monophyletic (Adkins et al., 2001; Madsen et al., 2001; Murphy et al., 2001a,b; Huchon et al., 2002). There is, however, some debate regarding the position of Rodentia relative to other mammalian orders in phylogenetic trees. Traditionally, the order Lagomorpha (hares, rabbits, and pikas) is considered to be most closely related to rodents (i.e., a sistergroup) based on their morphological similarity (Shoshani and McKenna, 1998) (Fig. 1-lA). The rodents and lagomorphs together comprise a clade termed Glires. Morphological similarities also link the elephant shrews (order Macroscelidea) as the sister-group to the Glires (Fig. 1-lA). Molecular studies have demonstrated markedly different relationships between many traditional mammalian orders, but they all agree that rodents and lagomorphs should be placed together (Huchon et al., 2001; Madsen et al., 2001; Murphy et al., 2001a,b) (Fig. 1-1B). The broadly based studies also agree in placing the Glires as sister-group to a clade containing primates (Madsen et al., 2001; Murphy et al., 2001a,b). In terms of dating the origin of the Rodentia, the superorder Glires likely originated between 64 and 104 million years ago (mya) (Archibald et al., 2001; Murphy et al., 200la). The diversification of rodents is therefore estimated at 65 mya at the earliest on the basis of both palaeontological (Alroy, 1999; Archibald et al., 2001) and molecular (Bromham et al., 1999; Foote et al., 1999; Eizirik et al., 2001) data. Thus, the predecessors of rodents may have coexisted with dinosaurs, but true rodents did not evolve until after the CretaceousTertiary Period boundary (i.e., 100, corresponding to 1 second). In contrast, a third category of rat ultrasonic vocalization has been referred to as a short call because of its relatively brief duration (