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.