Pavlov's Dogs

Total Page:16

File Type:pdf, Size:1020Kb

Pavlov's Dogs Magazine R117 Feature Pavlov’s dogs A pilgrimage to the last working place of the behavioral psychologist concept of associative learning Ivan Pavlov in Russia led to the discovery of a photograph album full of was born [6]. pictures of the original ‘Pavlov’s dogs’. Tim Tully explains how he While these studies were made this remarkable discovery, and how the photos have inspired the tremendously influential in their day naming of many new mutant fruitflies with defective memory — see the writings of the American phenotypes. behaviorist John Watson, for instance — their true impact has Eleven years ago, I began a Benzer’s lab at Cal Tech in the become apparent only now. In scientific mission with a trip to early 1970s. His graduate student, essence, Pavlov distilled the Russia, to find the names of Bill Harris, and an upstart new complexity of learned behavior Pavlov’s dogs. My intention was to postdoctoral student, W.G. ‘Chip’ down to one elemental component name Drosophila memory mutants Quinn, published in 1974 the first — a change in behavior produced after the dogs. At the time, valid claim for learning in by the association of two stimuli in however, two major impediments Drosophila by showing that flies time (bell and food, for instance). lay in the way of this high-minded could learn to avoid an odor when As such, the particular behavioral objective. I didn’t have many punished with footshock [2,3]. The response was no longer important, memory mutants and I could find Benzer lab then began a chemical making the procedure the name of but one of Pavlov’s mutagenesis to look for X-linked generalizable to other species and dogs, Bierka. My mission was to learning mutants, resulting in the tasks. With complete experimental change all that. So in the Spring of discovery by Duncan Byers of control over presentations of the 1992, I braved a trip to the Pavlov dunce [4], the first experimentally two stimuli, moreover, the Institute in Koltushi, a small village induced learning-defective animal functional properties of this outside of St. Petersburg, to in history. That effort got Quinn a elemental association could be rummage through the last place job at Princeton University, where quantified in detail. Throughout the that Pavlov worked. My efforts to he continued the behavioral rest of the 1900s, behavioral identify the dogs failed, and I was screen, successfully generating properties of Pavlovian learning ready to accept that their names additional mutants (see [5]). Quinn were quantified and compared would remain forever anonymous, decided to play on the word dunce across the animal kingdom, when a soft-spoken, lonely woman and gave these mutants names like revealing a ‘functional homology’ in an obscure museum dingy, daffy, dumbo, etc. When he ranging from insects (Drosophila, nonchalantly handed me 40 mentioned these names in a grant bee, cockroach) to mollusks photographs of Pavlov’s dogs, proposal to NIH, however, (Aplysia, Hermissenda) to names and all! Now, more than ten someone there objected to “the mammals (rodent, chick, primate, years later, we have completed a derogatory terms used to define human). large-scale behavioral screen, learning disabled animals”. Quinn How is this possible, given the identifying 60 new memory retaliated by renaming the mutants great diversity and complexity of mutants [1]. Mission complete. after vegetables — rutabaga, behavioral tasks and underlying Meet some of the namesakes of radish, turnip, cabbage, zucchini, neural circuitries observed in this ‘Pavlov’s flies’. ochre. Great sport! And, as Jeff wide range of species? The answer So what’s in a name? Hall once quipped, “You can’t must be that the behavioral Drosophologists have a tradition of dynamite an interesting name out properties of Pavlovian learning christening new mutants with fun of a nematologist”. reflect the cellular plasticity of and creative names. And, why not? So, does the name Pavlov ring a underlying neurons. Neurons in Finding the mutants in the first bell? Most of us know from college insects function much the same place usually involves a that Pavlov (1849–1936) was the way as neurons in mammals, for promethean struggle against famous Russian ‘psychologist’ who instance, and accumulating tedium, boredom and insecurity. devised a simple, elegant molecular biological evidence Often, the new names are experimental paradigm with which suggests a staggering level of descriptive — like stuck, to study learning. For several evolutionary conservation. So now dissatisfaction, cuckold or don repetitions, Pavlov would ring a bell we can see that Pavlov’s giovanni to describe mutants with just before giving food to a hungry conceptualization of an elemental defective courtship behavior. dog. Before long, he noticed, the form of associative learning Sometimes, labs develop themes dog started salivating whenever it provided an experimental ‘window’ around which to name mutants. heard the bell. Pavlov interpreted to link behavioral plasticity with One of my favorites concerns the this as indicating that the dog had neuronal plasticity. original set of learning mutants. learned to ‘associate’ the bell tone I began studying Pavlovian This effort began in Seymour with food reward and, thus, the learning as an undergraduate in Current Biology Vol 13 No 4 R118 Ten of the more photogenic of Pavlov's dogs. Krasavietz (upper left), Beck, Milkah, Ikar, Joy, Tungus, Arleekin, Ruslan, Toi and Murashka (bottom right). The rest of Pavlov's dogs and their corresponding Drosophila memory mutants can be found on the author's webpage at www.cshl.org. Jerry Hirsch’s laboratory at the — and I started thinking about Ivan Balaban, at the Institute of University of Illinois, where I Pavlov’s dogs. Higher Nervous Activity in Moscow investigated whether circadian Why his dogs? Well, obviously, I in 1988 to see if he could dig up rhythm influenced conditioning of must like dogs. Growing up in any more ‘bones’ among Pavlov’s the proboscis extension reflex in Midwest America, my brothers and original papers. From Pavlovian blow flies. Though Hirsch is most I hunted with field dogs and were Wednesdays. Isd. Akad. Nauk., famous for his studies of the constantly amazed at the power of Moscow (1949) vII (protocols of genetic bases of geotaxis [7,8], he selective breeding for retrievers, 1933–34years) Balaban uncovered was trained by the Berkeley pointers and sniffers. While newly 21 names of Pavlov’s dogs. Two of experimental psychologists, enamored with behavior-genetic the four memory mutants identified Tolman and Tryon, and primarily studies in graduate school, I from the Brandeis screen were was interested in the genetic basis bought a bassethound with the then appropriately christened, of learning. I found Hirsch’s intention to begin my own nalyot and golovan [14,15]. Four perspective on behavior-genetics breeding experiments for memory mutants, however, were fascinating and decided to stay on behavioral traits. In a somewhat not enough. For an emergent, for graduate school, working on twisted form of scholarship, I behavioral process like memory several aspects of associative and named my puppy after W.F.R. formation, many genes are likely to nonassociative learning in blow Weldon, a famous turn-of-the- be involved, clearly dictating more flies [9–11]. Full of Pavlov as a new century British geneticist who mutant screening and, accordingly, postdoctoral fellow in Quinn’s studied (among other things) the the likely need for more dog laboratory, I then focused on inheritance of coat color in names. developing a Pavlovian procedure bassethounds. To me, that had a I had just moved to Cold Spring for the Drosophila odor–shock certain conceptual ring to it, and it Harbor Laboratory in the Fall of avoidance task. A new ‘teaching gave Weldon a certain stature. 1991 with high hopes of machine’ and training protocol Weldon was still with me ten years marshalling the resources for a yielded robust initial learning later at Brandeis as I realized that large-scale mutant screen, when I scores with relatively long-lasting Pavlov must have liked his dogs was invited by Elena Savvateeva memory retention in normal flies enough to name them. This (now head of the Laboratory of and defective but detectable seemed like an interesting piece of Neurogenetics) and Nicholas memory retention in the original scientific history, in spite of the Kamyshev (now head of the vegetable mutants [12,13]. With more high-minded use I had Laboratory of Comparative this Pavlovian task, my fledgling concocted for the dogs’ names. Behavioral Genetics) to lecture at research group at Brandeis As mentioned above, my own the Pavlov Institute in Koltushi. I University initiated a small-scale literature search uncovered only accepted with relish, knowing that screen for memory mutants in 1987 Bierka. So, I wrote my colleague, such a trip may be my last chance Magazine R119 architecture in St. Petersburg. behavior in Drosophila Then, on the last day of my visit, melanogaster. Proc. Natl. Acad. Sci. U.S.A. 71, 707–712. Elena asked if I might like a private 3. Tully, T. (1984). Drosophila learning: tour of Pavlov’s home — behavior and biochemistry. Behav. Apartment #11, 7th Line on Genet. 14, 527–557. Vasilievsky Island. I was tired of 4. Dudai, Y., Jan, Y.-N., Byers, D., Quinn, W. and Benzer, S. (1976). touring and really didn’t want to dunce, a mutant of Drosophila go, but I had to be polite. To my melanogaster deficient in learning. eye, the place was run down. The Proc. Natl. Acad. Sci. U.S.A. 73, 1684–1688. curator, Dr. Nonna Volkova, was a 5. Quinn, W., Sziber, P.P. and Booker, pleasant, attractive woman, R. (1979). The Drosophila memory however, and insisted with mutant amnesiac. Nature 277, religious fervor that everything — 212–214.
Recommended publications
  • 2000 Highlights
    from the 2000 Annual Report HIGHLIGHTS OF THE YEAR The research and education programs at the Laboratory continue their strong momentum. The Watson School of Biological Sciences recruited its second class of students this year, and the DNA Learning Center underwent extensive renovations that will further its educa- tional objectives. The Meetings and Courses program and Banbury Center continue to be invaluable resources for scientific information, and the Cold Spring Harbor Laboratory Press added new projects and properties to its long list of titles. In this, the year of the Human Genome, Cold Spring Harbor Laboratory was a bustling center of scientific activity. Research Cancer Malignant melanoma is an aggressive, deadly cancer that does not respond to conventional chemotherapy. Other aggressive, chemoresistant can- cers—and approximately half of all cancers—are characterized by muta- tions in the p53 tumor suppressor gene. Malignant melanomas, however, do not typically display mutations in the p53 gene. To explore alternative explanations for the origins and properties of malignant melanoma, and to identify potential targets and strategies for therapy, Scott Lowe and his colleagues have examined the status of other genes known to function downstream from p53 in a pathway leading to Scott Lowe “apoptosis” or “programmed cell death.” When intact, this pathway rids the body of abnormal, precancerous cells by triggering a cellular self-destruct mechanism. When this pathway is disrupted (by the loss of p53 function, for example), precancerous cells sur- vive and proliferate, resulting in cancer. This year, Scott and postdoctoral fellow Marisol Soengas found that malignant melanomas often lose a key trigger of programmed cell death, a protein called Apaf-1 (apop- tosis activation factor-1).
    [Show full text]
  • Contributors
    Contributors Numbers in parentheses indicate the chapter contributed by authors. Carol A. Barnes (15) Paul E. Gold (7) Arizona Research Labs Departments of Psychology and Division of Neural Systems, Memory Psychiatry and Aging Neuroscience Program University of Arizona Institute for Genomic Biology Tucson, AZ 85724 University of Illinois Champaign, IL 61820 James E. Black (2) Department of Psychiatry William T. Greenough (2) Southern lUinois School of Medicine Beckman Institute Springfield, IL 62794 University of Illinois Urbana, IL 61801 Timothy J. Buschman (10) Picower Institute for Learning and Memory RIKEN-MIT Neuroscience Research Stephen C. Heinrichs (17) Center Department of Psychology Department of Brain and Cognitive Boston College Sciences Chestnut Hill, MA 02467 Massachusetts Institute of Technology Cambridge, MA 02142 Peter W. Kalivas (14) Department of Physiology Michael Davis (12) Medical University of South Carolina Department of Psychiatry Charleston, SC 29425 Emory University School of Medicine Atlanta, GA 30322 Raymond P. Kesner (8) Josh T. Dubnau (3) Psychology Department Cold Spring Harbor Laboratory University of Utah Cold Spring Harbor, NY 11724 Salt Lake City, UT 84112 Contributors Donna L. Korol (7) Tatsuya Ohyama (13) Department of Psychology Department of Neurobiology and Neuroscience Program Anatomy Institute for Genomic Biology University of Texas Medical School University of Illinois Houston, TX 77030 Champaign, IL 61820 Marsha R. Penner (15) Division of Neural Systems, Memory Ryan T. LaLumiere (14) and Aging Department of Neurosciences University of Arizona Medical University of South Carolina Tucson, AZ 85724 Charleston, SC 29425 Alison R. Preston (9) Department of Psychology Julie A. Markham (2) Neurosciences Program Beckman Institute Stanford University University of Illinois Stanford, CA 94305 Urbana, IL 61801 Corey B.
    [Show full text]
  • 1997 Highlights
    from the 1997 Annual Report research. The projects and thinking I have outlined are all essential for our research insti- tution to remain dynamic. At the same time, we must make sure that our scientists are supported to the fullest extent possible and that the research remains of the highest pos- sible quality, in the new academic style. HIGHLIGHTS OF THE YEAR Research Highlights Cancer Genetics and Cell Division In March, Cold Spring Harbor Laboratory (CSHL) scientists Michael Wigler and Clifford Yen with colleague Ramon Parsons, M.D., Ph.D., of the Herbert Irving Comprehensive Cancer Center and Columbia-Presbyterian Medical Center, announced the discovery of a tumor suppressor gene, which they named PTEN. The gene appears to be altered in a large percentage of brain, breast, and prostate cancers, and evidence suggests that loss of PTEN affects the way a benign tumor becomes malignant. Unlike mutations of genes such as hMSH2 and BRCA1, which were found in people who have hered- itary predispositions to cancer, PTEN was discovered by analyzing the more com- mon sporadic cancers. More than 80% of all cases of cancer are sporadic, mean- ing that they have no obvious hereditary contribution. PTEN received its name because of its similarity to phosphatases and tensin. The similarity between PTEN and protein phosphatases, which remove phosphates from proteins, is significant because many oncogenes—genes that help to trans- form normal cells into cancer cells—encode tyrosine kinases, which add phos- phates to proteins. Tensin is part of a complex of proteins that sits below the cell surface and controls cell shape.
    [Show full text]
  • Annual Report
    ANNUAL REPORT 1996COLD SPRING HARBORLABORATORY ANNUAL REPORT 1996 © 1997 by Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory P.O. Box 100 1 Bungtown Road Cold Spring Harbor, New York 11724 Website: http://www.cshl.org Managing Editor Susan Cooper Editorial staff Dorothy Brown, Annette Kirk Photography Margot Bennett, Ed Campodonico, Bill Dickerson, Marlene Emmons Typography Elaine Gaveglia, Susan Schaefer Cover design Margot Bennett Book design Emily Harste Front cover: Mushroom body neurons in the whole-mount Drosophila brain and the live fly head visualized by enhancer-trap driven expression of green fluorescent protein. These preparations allow electrophysiological and optic imaging analysis of identified neurons in whole brains or live flies. (Nicholas Wright, John Connolly, Tim Tully, Yi Zhong) Back cover: Laboratory's Library (Marlene Emmons) Section title pages: Marlene Emmons, Susan Lauter, Ed Campodonico, Bill Geddes Contents Officers of the Corporation/Board of Trustees v Governance and Major Affiliations and Committeesvi PRESIDENT'S ESSAY 1 DIRECTOR'S REPORT 21 ADMINISTRATION REPORT 52 RESEARCH Tumor Viruses60 Molecular Genetics of Eukaryotic Cells84 Genetics108 Structure and Computation145 Neuroscience170 CSH Laboratory Fellows 196 Author Index206 COLD SPRING HARBOR MEETINGS AND COURSES Academic Affairs 210 Symposium on Quantitative Biology 212 Meetings214 Postgraduate Courses237 Seminars276 Undergraduate Research278 Nature Study280 BANBURY CENTER Director's Report282 Meetings287 DNA LEARNING CENTER 309 COLD SPRING HARBOR LABORATORY PRESS 326 FINANCE Financial Statements 332 Financial Support335 Grants335 Methods of Contributing 343 Capital and Program Contributions 344 Child Care Center Capital Campaign 345 Annual Contributions346 LABORATORY STAFF 356 Standing (from left): L.B. Polsky, J.P. Cleary, W.E. Murray, J.A.
    [Show full text]
  • Beyond Therapy: Biotechnology and the Pursuit of Happiness
    BBBEEEYYYOOONNNDDD TTTHHHEEERRRAAAPPPYYY BEYOND THERAPY BIOTECHNOLOGY AND THE PURSUIT OF HAPPINESS A Report of The President’s Council on Bioethics Washington, D.C. October 2003 www.bioethics.gov v CONTENTS LETTER OF TRANSMITTAL TO THE PRESIDENT xi MEMBERS OF THE PRESIDENT’S COUNCIL ON BIOETHICS xv COUNCIL STAFF AND CONSULTANTS xvii PREFACE xix 1 BIOTECHNOLOGY AND THE PURSUIT OF HAPPINESS 1 I. THE GOLDEN AGE: ENTHUSIASM AND CONCERN 4 II. THE CASE FOR PUBLIC ATTENTION 7 III. DEFINING THE TOPIC 10 IV. ENDS AND MEANS 11 V. THE LIMITATIONS OF THE “THERAPY VS. ENHANCEMENT” DISTINCTION 13 VI. BEYOND NATURAL LIMITS: DREAMS OF PERFECTION AND HAPPINESS 16 VII. STRUCTURE OF THE INQUIRY: THE PRIMACY OF HUMAN ASPIRATIONS 20 VIII. METHOD AND SPIRIT 21 ENDNOTES 24 2 BETTER CHILDREN 25 I. IMPROVING NATIVE POWERS: GENETIC KNOWLEDGE AND TECHNOLOGY 28 A. AN OVERVIEW 28 B. TECHNICAL POSSIBILITIES 30 1. Prenatal Diagnosis and Screening Out. 32 2. Genetic Engineering of Desired Traits (“Fixing Up”). 35 3. Selecting Embryos for Desired Traits (“Choosing In”). 38 C. ETHICAL ANALYSIS 42 1. Benefits. 44 vi CONTENTS 2. Questions of Safety. 45 3. Questions of Equality. 49 4. Consequences for Families and Society. 51 II. CHOOSING SEX OF CHILDREN 55 A. ENDS AND MEANS 57 B. PRELIMINARY ETHICAL ANALYSIS 59 C. THE LIMITS OF LIBERTY 64 D. THE MEANING OF SEXUALITY AND PROCREATION 66 III. IMPROVING CHILDREN’S BEHAVIOR: PSYCHOTROPIC DRUGS 69 A. BEHAVIOR MODIFICATION IN CHILDREN USING STIMULANTS 72 1. What Are Stimulant Drugs? 75 2. Behaviors Inviting Improvement through Stimulant Drugs. 77 3. The “Universal Enhancer.” 81 B.
    [Show full text]
  • Discovery of Genes Involved with Learning and Memory
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 13460–13467, November 1996 Colloquium Paper This paper was presented at a colloquium entitled ‘‘Memory: Recording Experience in Cells and Circuits,’’ organized by Patricia S. Goldman-Rakic, held February 17–20, 1996, at the National Academy of Sciences in Irvine, CA. Discovery of genes involved with learning and memory: An experimental synthesis of Hirschian and Benzerian perspectives (DrosophilaymutantycAMPyCREByPavlovian conditioning) TIM TULLY Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724 ABSTRACT The biological bases of learning and memory Behavior-Genetic Analysis of Polygenic Architecture are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction Under the intellectual guidance of Tolman and Tryon (5) at produced by gene disruptions. This perspective derives both the University of California at Berkeley, Jerry Hirsch studied from early ‘‘genetic dissections’’ of learning in mutant Dro- the extreme responses of maze-bright and maze-dull rats to sophila by Seymour Benzer and colleagues and from earlier elucidate theories of learning. Afterwards, Hirsch crossed behavior-genetic analyses of learning and in Diptera by Jerry paths with Dobzhansky at Columbia University (New York) Hirsch and coworkers. Three quantitative-genetic insights and integrated his views of population genetics with those of derived from these latter studies serve as guiding principles experimental psychology (6, 7). This Hirschian view of ‘‘mod- for the former. First, interacting polygenes underlie complex ern’’ behavior-genetic analysis is best described in the epilogue traits. Consequently, learningymemory defects associated of Behavior-Genetic Analysis (8), which stands as one of the with single-gene mutants can be quantified accurately only in most comprehensive syntheses of the conceptual issues.
    [Show full text]
  • Highlights of the Year
    from the 1994 Annual Report HIGHLIGHTS OF THE YEAR Research Highlights Our research programs in cancer biology, plant genetics, neurobiology, computational biology, and structural biology all saw significant progress this year. In cancer research, some of the most exciting work came from David Beach’s laboratory. In 1993, David’s group discovered the first members of a new family of cancer-related genes. Called cy- clin-dependent kinase inhibitors, the proteins made by these genes inhibit a major class of proteins, the cyclin-dependent kinases, which are the key regulators of the cell divi- sion cycle. The first two of these proteins called p16INK and p21 were the founders of two different families of growth regulators that have grown during the last year. The p16INK gene is altered in a wide variety of human tumors, suggesting that it acts as a tumor suppressor, and a new member of this family has been demonstrated to be induced by an extracellular growth inhibitor called tumor growth factor ß· In other work, the Beach laboratory has linked signal transduction through the RAS pathway to control of the cell cycle by cyclin-dependent kinases, via a known regulatory protein called cdc25. In col- laboration with the Beach laboratory, Bruce Stillman’s group has shown that the p21 cell proliferation inhibitor has a dual role in cell cycle regulation. The p21 protein inhibits DNA replication via its interaction with proliferating cell nuclear antigen (PCNA), an es- sential protein required for DNA replication and DNA repair, but interestingly, it still al- lows DNA repair. The gene encoding the p21 protein is activated by the well-known tumor suppressor protein p53.
    [Show full text]
  • Ethics in America II Discussion Guide
    TABLE OF CONTENTS INTRODUCTION ………………………………………………………………………………………… i 1. DOING GOOD AND AVOIDING EVIL: Fundamentals of Philsophical Ethics ......................................... 1 2. THE THEORY BEHIND THE PRACTICE: Why We Choose the Right and Refuse the Wrong.............41 3. CHOOSING JUSTICE: Elections and Judicial Independence............................................................................59 4. THREE FAREWELLS: Medicine and the End of Life........................................................................................90 5. WAR STORIES: National Security and the News ...............................................................................................120 6. MY BROTHER'S KEEPER: Personal Ethics......................................................................................................149 7. A BETTER BRAIN: The Ethics of Neuro-enhancement..................................................................................182 8. RISK, REWARD, RESPONSIBILITY: Ethics in Business...............................................................................217 INTRODUCTION Welcome to Ethics in America II. As with the original Ethics in America—brilliantly conceived and launched by the late Fred Friendly, Edward R. Murrow Professor at Columbia University’s School of Journalism—this six-part series of programs and accompanying materials covers diverse topics of public, private, and professional ethics. It will be broadcast on public television, available as DVDs, and can be found on the Annenberg Media
    [Show full text]