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Synaptic Tagging and Capture Synaptic Tagging and Capture Sreedharan Sajikumar Editor Synaptic Tagging and Capture From Synapses to Behavior Editor Sreedharan Sajikumar Yong Loo Lin School of Medicine Department of Physiology National University of Singapore Singapore , Singapore ISBN 978-1-4939-1760-0 ISBN 978-1-4939-1761-7 (eBook) DOI 10.1007/978-1-4939-1761-7 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2014951217 © Springer Science+Business Media New York 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Pref ace Synaptic tagging was fi rst proposed by Frey and Morris in 1997 and is now widely referred to as synaptic tagging and capture (STC). STC provides a conceptual basis for how short-term memory is transformed into long-term memory in a time- dependent fashion. The idea of publishing a book on STC was conceptual- ized during the Eighth Federation of European Neuroscience Societies (FENS) meeting held on July 14–18, 2012, in Barcelona, Spain. We had a symposium on tagging covering the latest developments in the fi eld, chaired by Richard Morris. The focus of this book is on STC and it is intended to inform the reader about the current understanding of STC, 17 years after its fi rst discovery. The book provides a unique opportunity for beginners in the fi eld to have a deeper understanding of and to navigate the complexities of long-term associative memory mechanisms. The book is divided into two parts: the fi rst part provides a detailed picture about the cellular aspects of STC while the second part deals with metaplastic and behavioural views. Therefore, as a whole, a wide-ranging view of STC from syn- apses to behaviour is encapsulated. Writing a book chapter is not an easy task especially in a scientifi c world dominated by Impact Factors . I would like to warmly thank the authors for their willingness and commitment to contribute to this book as their efforts will con- tribute significantly to the excellent intellectual discourse in this exciting area of memory research. I am extremely fortunate to have short introductions from Prof. Richard Morris and Prof. Wickliffe Abraham for this book found in parts 1 and 2, respectively. At the time of writing, I realized that more than a year has passed since I started this book project. I appreciate the patience of many of the authors. I would like to thank the Neuroscience section editor, Simina Calin, and Development Editor, Portia F. Wong, for their patience and guidance during this project, and all of the editorial staff at Springer, New York, for their patience and professionalism. In addi- tion, the great support that I received during my career and for this project and from v vi Preface the pioneers in the fi eld is acknowledged here: Prof. Julietta U. Frey, Prof. Martin Korte, Prof. Wickliffe Abraham, Prof. Richard Morris, and Prof. Todd Sacktor. It has been a rewarding professional and personal experience for me and I hope that all the readers will fi nd something valuable in this book. Singapore Sreedharan Sajikumar Part I: Introduction The concept of ‘synaptic tagging and capture’ (STC) that is the subject of this book arose in the course of experimental studies of protein synthesis-dependent long- term potentiation (LTP) during the mid-1990s. The ramifi cations of the original idea, and the way it has developed through the creative research of numerous scien- tists around the world, have now extended well beyond the immediate aims of the original research. As this timely book amply testifi es, the concept of STC is leading us into new realms of thinking about synaptic plasticity, dendritic integration within neurons, and the neural basis of learning and memory. Having conducted research in the late 1980s revealing the role of the N -methyl- d -aspartate receptor in memory encoding for spatial information (Morris et al. 1986), I became interested in the role of activity-dependent synaptic plasticity in learning and memory. Collingridge et al. (1983) had established the necessity of NMDA receptor activation for the induction of LTP, a physiological phenomenon with intriguing properties that might be relevant for memory. This led in turn to refl ecting on the possibility that the temporal persistence of LTP might be one deter- minant (though not the only one) of the persistence of memory itself-an idea that Barnes (1979) was already developing in the studies of ageing. This line of thinking led me to the important work of the Magdeburg group led originally by Hans- Juergen Matthies who were early advocates of the idea that long-term plasticity and long-term memory both require protein synthesis. I read several of the groups’ papers but found myself puzzled by something left out in their arguments. If the relevant protein synthesis were to be somatic, how do the synthesized proteins fi nd their way to the correct synapses? That is, how do they target the very synapses that have recently been subject to the early or post-translational form of LTP? It occurred to me that the ‘plasticity related proteins’ (PRPs) that were synthesized in response to strong patterns of tetanic stimulation in LTP experiments, or to strong natural stimulation during learning, might have the potential of being shared around the dendrites of the neuron but only used as required. I visited Magdeburg in 1995 and discussed this question with Uwe Frey (later, Julietta Frey) who immediately grasped its signifi cance. I put to her the prediction that, in an LTP experiment, a second independent pathway tetanized in the presence vii viii Part I: Introduction of anisomycin might still show protein synthesis-dependent late-LTP if an independent pathway had been tetanized shortly beforehand. I thought about our discussion in the weeks and months that followed but, unknown to me, Julietta began experiments herself and found this prediction to be upheld. She came to Edinburgh to give a talk and shared with me the by then quite extensive set of data that she had collected. It was a magical moment. We discussed some other ideas for experiments together, but all the credit for the original experimental work rests entirely with her. We prepared the fi nal version of the manuscript together in one of the great coffee shops of the former East-German world, beside the Opera House on Unter den Linden in Berlin, and then tried our luck at Nature . The refereeing was fair but tough, as it generally is, and one of the experiments in the fi nal paper was actually suggested by one of the referees. The paper was published (Frey and Morris 1997) and we both felt the paradox that protein synthesis-dependent LTP could actually be induced during the inhibition of protein synthesis was an observation that could tell us something important about neural function. But what was it telling us and what did it mean? Frey and I argued, in a strictly abstract and conceptual manner, that the induction of LTP above a certain minimum threshold would, in addition to increasing synaptic strength temporarily, set a ‘tag’ that had the function of sequestering or ‘capturing’ plasticity proteins (Frey and Morris 1997). Thus, the tag was set locally, refl ected the input specifi city of LTP, and was induced by a post-translational mechanism. However, given the presence of this tag, the synthesis and distribution of PRPs could afford to be more global. Synthesis could perhaps be somatic, but with PRPs distributed all over the neuron even though they would only be captured at sites that had recently undergone poten- tiation. Only later was the concept of dendritic protein synthesis really developed. With the exception of a few labs, including Eric Kandel’s group at Columbia who conducted similar studies in Aplysia neurons in culture (Martin et al. 1997) and that of Doug Fields and Serena Dudek at NIH (Dudek and Fields 2002), there was little initial interest in STC. Frey’s group pressed on, and in a series of brilliant stud- ies, many conducted in Magdeburg by the editor of this book, Sreedharan Sajikumar, further properties of STC were identifi ed.
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