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working scientists from the graduate student level up- wards who apply PCR to problems in human, animal and plant , cell , diagnostics, and molecular .

CONTENTS PERSPECTIVES James D. Watson, Cold Spring Harbor Laboratory Kary Mullis, AN IN-DEPTH LOOK AT PCR Primers, Oligos and Hybridization Wojciech Rychlik, National Biosciences, Inc. Biology of DNA Polymerases Tom Kunkel, National Institutes of Health ~ ii~~ ~ PCR Automation and Genotyping Stanley Rose, The Perkin-Eimer Corporation APPLICATIONS OF PCR Glen A. Evans, University of Texas A Decade of PCR Human Genetics Henry Erlich, Roche Molecular Systems Cold Spring Harbor Laboratory and The Perkin- Molecular Diagnostics Elmer Corporation celebrate 10 years of amplifica- Tom Caskey, Baylor College of Medicine tion with a videotape library in which Forensic Analysis winners Kary Mullis and and 19 other Bruce Budowle, FBI Academy distinguished scientists review the applications and Gene Evolution/Ancient DNA evolution of the amplification technique hailed as one Svante P~i~ibo, University of Munich of the century's most important scientific tools. Agriculture and the Third World Richard Jefferson, CAMBIA In 1995, the polymerase chain reaction will be 10 Gene Expression in Single Cells years old. The technique that began as a late-night in- Jim Eberwine, University of Pennsylvania spiration by an unrenowned scientist is now the bed- In Situ PCR rock of DNA research, gene discovery, diagnostics Ashley Haase, University of Minnesota development, forensic investigation and environmen- Combinational Libraries and Rapid Evolution tal science. It has built an industry, provoked a court Andrew Ellington, Indiana University case, and spawned a dozen books, countless papers THE FUTURE OF PCR and a journal. Along the way, it earned its inventor, Applications of Long Distance PCR Kary Mullis, a Nobel prize~ Elise Rose, The Perkin-Elmer Corporation PCR Quantitation To mark this anniversary, a conference sponsored Francois Ferre, The Immune Response Corporation by The Perkin-Elmer Corporation was held at Cold Analysis of PCR Products in Microchips Spring Harbor Laboratory in September 1994. Begin- Stephen Fodor, Affymetrix, Inc. ning with perspectives from James Watson, famed RNA Differential Display for the discovery of the structure of DNA, and PCR- Peng Liang, Dana Farber Cancer Institute inventor Kary Mullis, outstanding scientists from a Representational Difference Analysis variety of fields reviewed the impact of the technique Nikolai Lisitsyn, Cold Spring Harbor Laboratory on their specialties, discussing the present and future Summary applications of PCR technology. Maynard Olson, University of Washington A day and a half of wide-ranging, highly il- 1994, 7 edited videotapes (10 hours 15 minutes in total) lustrated talks have been captured in this unique VHS: ISBN 0-87969-473-4; PAL: ISBN 0-87969-474-2 videotape library. The collection will appeal to Price: $300 Editor John H. Byrne (Houston) Managing Editor Judy Cuddihy (Cold Spring Harbor)

Editorial Board

Per Anderson (Oslo) Peter Holland (Durham) Philippe Ascher (Paris) Eric Kandel (New York) Jocelyne Bachevalier (Houston) Lawrence C. Katz (Durham) Alan D. Baddeley (Cambridge) Mary B. Kennedy (Pasadena) Carol A. Barnes (Tucson) Joseph Le Doux (New York) Timothy Bliss (London) Stephen G. Lisberger (San Francisco) Thomas J. Carew (New Haven) Nicholas J. Mackintosh (Cambridge) Graham Collingridge (Birmingham) Daniel Madison (Stanford) John Connor (Albuquerque) Roberto Malinow (Cold Spring Harbor) Thomas Curran (Memphis) Randolf Menzel (Berlin) Antonio Damasio (Iowa City) Mortimer Mishkin (Bethesda) Michael Davis (New Haven) Richard Morris (Edinburgh) Ronald Davis (Houston) Dennis D.M. O'Leary (La Jolla) Pietro De Camili (New Haven) Marcus Raichle (St. Louis) Yadin Dudai (Rehovot) Christine Sahley (West Lafayette) Howard Eichenbaum (Stony Brook) Daniel Schacter (Cambridge) Yves Fr~gnac (Gif sur Yvette) James Schwartz (New York) Alan Gelperin (Murray Hill) Carla Shatz (Berkeley) Alison Goate (St. Louis) Wolf Singer (Frankfurt) Patricia Goldman-Rakic (New Haven) Larry Squire () Michael E. Greenberg (Boston) Charles Stevens (La Jolla) Stephen Heinemann (La Jolla) Richard Thompson (Los Angeles) Martin Heisenberg (Wurzburg) Richard Tsien (Stanford) Susan Hockfield (New Haven) Tim Tully (Cold Spring Harbor) Editorial Offices Editorial/Production Cold Spring Harbor Laboratory Press Nadine Dumser, Technical Editor 1 Bungtown Road Kristin Kraus, Production Editor Cold Spring Harbor, New York 11724 Cindy Grimm, Production Assistant Phone (516) 367-8492 Doris Lawrence, Editorial Secretary Fax (516) 367-8532

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Review

Prediction and Preparation, Fundamental Functions of the Cerebellum ...... 1 Eric Courchesne and Greg Allen

Research papers

Impaired Capacity of Cerebellar Patients to Perceive and Learn Two-Dimensional Shapes Based on Kinesthetic Cues ...... 36 Yury Shimansky, Marian Saling, David A. Wunderlich, Vlastislav Bracha, George E. Stelmach, and James R. Bloedel

Lateral Cerebeilar Hemispheres Actively Support Sensory Acquisition and Discrimination Rather Than Motor Control ...... 49 Lawrence M. Parsons, James M. Bower, Jia-Hong Gao, Jinhu Xiong, Jinqi Li, and Peter T. Fox

Cerebellar Guidance of Premotor Network Development and Sensorimotor Learning ...... 63 Sherwin E. Hua and James C. Houk

Role of Cerebellum in Adaptive Modification of Reflex Blinks ...... 77 John J. Pellegrini and Craig Evinger

Single-Unit Evidence for Eye-Blink Conditioning in Cerebellar Cortex is Altered, but Not Eliminated, by lnterpositus Nucleus Lesions ...... 88 Donald B. Katz and Joseph S. Steinmetz

Effect of Varying the Intensity and Train Frequency of Forelimb and Cerebellar Mossy Fiber Conditioned Stimuli on the Latency of Conditioned Eye-Blink Responses in Decerebrate Ferrets ...... 105 Piir Svensson, Magnus Ivarsson, and Germund Hesslow

Conditioned Response Timing and Integration in the Cerebellum ...... 116 John W. Moore and June-Seek Choi

A Model of Pavlovian Eyelid Conditioning Based on the Synaptic Organization of the Cerebellum ...... 130 Michael D. Mauk and Nelson H. Donegan Local Dendritic Ca z§ Signaling Induces Cerebellar Long-Term Depression ...... 159 Jens Eilers, Hajime Takechi, Elizabeth A. Finch, George J. Augustine, and Arthur Konnerth

Absence of Cerebellar Long-Term Depression in Mice Lacking Neuronal Nitric Oxide Synthase ...... 169 Varda Lev-Ram, Zuryash Nebyelul, Mark H. Ellisman, Paul L. Huang, and Roger Y. Tsien

Cover Dissociation of cerebellar attention (yellow and blue) and motor (green and red) activation (yellow and green -- overlap in activation of 3 or more subjects; blue and red = overlap of any 2 subjects). Three- dimensional volume rendering of the cerebellum and brain stem demonstrates that during an attention task, the most common site of activation was in the left superior posterior cerebellum, while during a motor task, the most common site was in the right anterior cerebellum. (For details, see Courchesne and Allen, p. 1; image rendered using VoxelView 2.5.) The following articles appeared last month in the first special issue devoted to learning and the cerebellum, Learning & Memory, vol. 3, number 6, March/April 1997

Review

The Cerebellum, LTD, and Memory: Alternative Views Rodolfo Llinfis, Eric J. Lang, and John P. Welsh Research papers

Preserved Performance by Cerebellar Patients on Tests of Word Generation, Discrimination Learning, and Attention Laura L. Helmuth, Richard B. Ivry, and Naomi Shimizu A Neural Model of Cerebellar Learning for Arm Movement Control: Cortico-Spino-Cerebellar Dynamics Jose L. Contreras-Vidal, Stephen Grossberg, and Daniel Bullock Multiple Subclasses of Purkinje Cells in the Primate Floccular Complex Provide Similar Signals to Guide Learning in the Vestibulo-ocular Reflex Jennifer L. Raymond and Stephen G. Lisberger The Effects of Reversible Inactivation of the Red Nucleus on Learning-Related and Auditory-Evoked Unit Activity in the Pontine Nuclei of Classically Conditioned Rabbits M. Claire Cartford, Elizabeth B. Gohl, Maria Singson, and David G. Lavond The Learning-Related Activity That Develops in the Pontine Nuclei During Classical Eye-Blink Conditioning Is Dependent on the interpositus Nucleus Robert E. Clark, Elizabeth B. Gohl, and David G. Lavond Reversible Inactivation of the Cerebellar Interpositus Nucleus Completely Prevents Acquisition of the Classically Conditioned Eye-Blink Response David J. Krupa and Richard F. Thompson Acquisition of a New-Latency Conditioned Nictitating Membrane Response--Major, But Not Complete, Dependence on Ipsilateral Cerebellum Christopher H. Yeo, Dominic H. Lobo, and Alison Baum Persistent Phosphorylation Parallels Long-Term Desensitization of Cerebellar Purkinje Cell AMPA-Type Glutamate Receptors Kazutoshi Nakazawa, Sumiko Mikawa, and Masao Ito