Decoding Neural Circuit Structure and Function

Transcription

1 Decoding Neural Circuit Structure and Function

2 Arzu Çelik Mathias F. Wernet Editors Decoding Neural Circuit Structure and Function Cellular Dissection Using Genetic Model Organisms 123

3 Editors Arzu Çelik Department of Molecular Biology and Genetics Boğaziçi University Bebek, Istanbul Turkey Mathias F. Wernet Fachbereich Biologie, Chemie, Pharmazie, Institut für Biologie Neurobiologie Freie Universität Berlin Berlin Germany ISBN ISBN (ebook) DOI / Library of Congress Control Number: Springer International Publishing AG 2017, corrected publication 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms 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. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

4 Foreword We Live in Exciting Times We live in exciting times. Blocking or activating single cell types and recording from them in the awake behaving animal has so much become standard that one could almost forget that it has not always been this way. In fact, it is only about 20 years ago that the usual way to establish structure function relationship e.g. in Drosophila was to screen randomly generated mutants. If the screen was a structural one, it was followed by behavioral tests, if the screen was a behavioral one, it was followed by a structural study. Much brain power went into ingenious design of these screens as well as in the elegant behavioral setups, many of them are still in use today. While the results obtained this way were certainly an interesting first step, they suffered from important limitations insurmountable at that time. First of all, the resolution one obtained was a course one, far away from the single cell level: a certain brain structure was found to be involved in a certain behavior, but which type of neuron was doing what job and how could not be answered. Another almost lethal disadvantage of Drosophila these days was the fact that the nervous system of Drosophila was silent for the investigator: except for the giant descending neuron, no neuron in the CNS could be recorded from. So how could one go further to disentangle a neural circuit, even when given a complete catalogue of neuron types from Golgi staining? Those were the days when the leech, lobster, and stick insects dominated the field of neural oscillators, when honeybees, silk moths, and cockroaches were model organisms for insect olfaction, precise timing was studied in barn owls, bats, and weakly electric fish and Aplysia was the hot spot for synaptic plasticity. One just needs to open a textbook on Neuroethology from the 1980s in order to see that. Interestingly, mammals seemed to be almost entirely excluded from this field since, except for place cells, their brain was studied mostly in anesthetized animals. As a systems neuroscientist working with Drosophila and submitting a paper to a major journal, one had to be prepared to receive reviews that started with A beautiful study, and ended with a rejection by saying if only it had been done in the v

5 vi Foreword right animal. By now, many of the aforementioned model organisms have been ousted by Drosophila, the mouse and the zebrafish, as exemplified in this book. But not only have the favorite animal species changed and new tools have been developed: the genetic revolution also led to a merger of different fields and cultures, bringing together people with different backgrounds. Nowadays, an advanced neuroscience student might have done some PCR in the morning, while after lunch, he/she goes on and pulls electrodes or prepares for calcium recording under the 2-Photon microscope. If I should name a few areas in the fly brain where this has led to unforeseen progress in our understanding, I would list olfactory processing and memory formation in the mushroom bodies, neural circuit for motion vision and the fly s inner compass within the central complex. What made the change? Genetically addressable neurons are the first and most important prerequisite, whether it be through the cell-specific promotors available for olfactory receptor neurons or via cell-specific enhancers further refined by intersectional expression strategies like split-gal4. Next are genetically encoded calcium indicators, kicked off by Roger Tsien with the famous paper Miyawaki et al, 1997 that opened the door to optical recording from every neuron you wanted. Proteins to block or activate identified neurons, like Shibire and Channelrhodopsin, represent other key ingredients to the success of the genetic approach. Of course, the combination of driver and effector flies mostly rests on the binary expression system Gal4-UAS, introduced by Brand and Perrimon in This book represents a beautiful collection of studies where the neural circuits for different types of behavior are dissected in genetic model organism using state-of-the-art tools from genetics, physiology, and computational analysis. Now that we have everything we ever dreamed of, we are mostly limited by our imagination and intellect if we fail, we have no excuse. Alexander Borst Max-Planck-Institute of Neurobiology Martinsried, Germany

6 Contents Part I Anatomy: High-Resolution Neuroanatomy Using Molecular-Genetic Tools 1 The Current State of the Neuroanatomy Toolkit in the Fruit Fly Drosophila melanogaster Daryl M. Gohl, Javier Morante and Koen J.T. Venken 2 Retinal Connectomics Kevin L. Briggman 3 Recent Progress in the 3D Reconstruction of Drosophila Neural Circuits Kazunori Shinomiya and Masayoshi Ito 4 Connectivity and Circuit Architecture Using Transsynaptic Tracing in Vertebrates Kazunari Miyamichi and Lindsay A. Schwarz 5 Live Imaging of Connectivity in Developing Neural Circuits in Drosophila Mehmet Neset Özel and Peter Robin Hiesinger Part II Behavior: The Behavioral Contributions of Identified Cell Types 6 Manipulation of Neural Circuits in Drosophila Larvae Ibrahim Tastekin and Matthieu Louis 7 Targeted Manipulation of Neuronal Activity in Behaving Adult Flies Stefanie Hampel and Andrew M. Seeds 8 Paradigms for the Quantification of Behavioral Responses in Zebrafish Chiara Cianciolo Cosentino and Stephan C.F. Neuhauss vii

7 viii Contents 9 The Use of Computational Modeling to Link Sensory Processing with Behavior in Drosophila Jan Clemens and Mala Murthy 10 Motor-Driven Modulation in Visual Neural Circuits Terufumi Fujiwara and Eugenia Chiappe 11 Causal Circuit Explanations of Behavior: Are Necessity and Sufficiency Necessary and Sufficient? Alex Gomez-Marin Part III Physiology: Visualizing the Activity of Identified Circuit Elements 12 Visualization of Synapses and Synaptic Plasticity in the Drosophila Brain Thomas Riemensperger, Florian Bilz and André Fiala 13 Whole-Brain Imaging Using Genetically Encoded Activity Sensors in Vertebrates Andreas M. Kist, Laura D. Knogler, Daniil A. Markov, Tugce Yildizoglu and Ruben Portugues 14 Understanding Mood Disorders Using Electrophysiology and Circuit Breaking He Liu and Dipesh Chaudhury 15 Combining Anatomy, Measurements and Manipulation of Neuronal Activity to Interrogate Circuit Function in Drosophila Yvette E. Fisher and Thomas R. Clandinin Part IV Development: The Molecular Determinants of Cell Type Diversity 16 Generation of Neuronal Diversity in the Peripheral Olfactory System in Drosophila Catherine Hueston and Pelin C. Volkan 17 The Developmental Origin of Cell Type Diversity in the Drosophila Visual System Claire Bertet 18 Single-Cell Transcriptomic Characterization of Vertebrate Brain Composition, Development, and Function Bosiljka Tasic, Boaz P. Levi and Vilas Menon

8 Contents ix 19 Transcriptional Profiling of Identified Circuit Elements in Invertebrates Marta Morey Part V Epilogue: Future Outlook and Challenges in the Field of Circuit Science 20 Perspective: A New Era of Comparative Connectomics Ian A. Meinertzhagen Erratum to: Single-Cell Transcriptomic Characterization of Vertebrate Brain Composition, Development, and Function... E1 Bosiljka Tasic, Boaz P. Levi and Vilas Menon

9 Notes from the Editors The idea for this book project was born after a very successful EMBO workshop of almost the same name: Decoding Neural Circuit Structure and Function. Organized by Arzu Çelik (Boğaziçi University), Nilay Yapici (then Rockefeller University, now Cornell University), and Hernan Lopez-Schier (Helmholtz Zentrum Muenchen) this workshop took place from September 26 to 28, 2014 on the wonderful campus of Boğaziçi University right in the center of the buzzing metropolis Istanbul. What makes meetings like this one so exciting is the interdisciplinary nature of the presentations, the very different backgrounds of the participating people, and the broad range of topics and techniques covered. Also, while teaching courses on neural circuit structure and function both in Istanbul and Berlin, we noticed that teaching material about this exciting and fast evolving area of research is under-represented. This book now intends to give a glimpse of what is currently possible. At the center of many questions lies the concept of a neuronal cell type and the question about its role within the brain in general, and within a more restricted neural circuit linked to a particular function. The progress toward reproducibly labeling neuronal cell types using molecular genetic tools in different genetic model organisms has been a major step forward over the last two decades. We are very happy that Alexander Borst has agreed to contribute a preface to this book project, in which he describes the impact that this truly historic ascension of genetic model organisms has had on a field that suffered from numerous technical challenges. The model systems we ended up focusing on in this book are the fruit fly, zebrafish, and the mouse. We apologize that the worm C. elegans ended up somewhat under-represented in our project that was not at all intended, but instead resulted from a series of unfortunate coincidences, when several authors had to drop out at the last minute. So, how does one organize 20 Chapters on The Structure and Function of Neural Circuits? In this book project, we decided to cover four large areas, which we think together represent the Neural Circuit field using genetic model organisms: Anatomy, Behavior, Physiology, and cell type specification (Development). xi

10 xii Notes from the Editors In Part I (Anatomy), the authors cover an amazing range of topics, beginning with an introduction to the complexity of molecular genetic toolkits, which can certainly seem intimidating (Chap. 1). Two chapters then present different efforts to reconstruct neural circuits in 3D using electron microscopy as well as light microscopy (Chaps. 2 and 3). Additional aspects of connectivity are also addressed: Trans-synaptic tracing using neurotropic viruses (Chap. 4), as well as live imaging of neural circuit formation (Chap. 5). Part II (Behavior) then moves on to describe the manipulation of cellular elements and the resulting consequences on animal behavior, both in fly larvae (Chap. 6), as well as adults (Chap. 7). The quantitative study of vertebrate behavior is also covered by discussing the visual responses of zebrafish (Chap. 8). In the following chapter, the important link between genetic manipulations, behavioral responses, and the computations executed by identified neural circuits are discussed (Chap. 9). The final two chapters remind us that nothing is set in stone and remains unchanged forever and describe the modulation of neural circuitry (Chap. 10), as well as the important question about what kind of problems can arise from drawing conclusions about the necessity or sufficiency of identified circuit elements purely from genetic manipulations in behaving animals (Chap. 11). Part III (Physiology) then presents important examples for how genetically encoded indicators of neuronal activity can be used to probe the nervous system of flies (Chap. 12), as well as the entire zebrafish brain (Chap. 13). This is followed by a chapter describing how the neural circuits affected in mood disorders can be studied in the mouse, using a combination of electrophysiology and optogenetics (Chap. 14). Finally, the fly visual system serves as an elegant example for how many of the so far covered techniques can be combined to reveal the cellular basis for motion computation in the invertebrate brain (Chap. 15). The question how the vast diversity in neuronal cell types is generated will be addressed in Part IV (Development). This Part starts with two examples for how neuronal cell fate decisions are regulated in different sensory systems of fruit flies (Chaps. 16 and 17). The investigation of neuronal cell types using transcriptomic approaches is addressed in two complementary chapters: One covers single cell transcriptomics in the mouse (Chap. 18), and the other one covers different transcriptomic approaches in invertebrates (Chap. 19). In summary, the four parts aim toward providing a holistic description of the role of identified cell types within neural circuits. It must be pointed out that many of the techniques and approaches described above become increasingly intertwined: many laboratories are implementing them simultaneously, resulting in impressive datasets of unprecedented precision. Nevertheless, the need for such synergy also presents important challenges: how can one single laboratory unite all the necessary expertise, the required funds, and equipment? It is not surprising that several large research centers have been established, where such environments are being provided: Janelia Research Campus, The Allen Brain Institute, The Champalimaud Center for the Unknown, and the Max-Planck Institute for Neurobiology, just to name a few prominent examples. We are particularly happy to unite authors from all these institutions within this book project.

11 Notes from the Editors xiii Where do we go from here? The complexity of neural circuit architecture and function that is arising from the efforts presented in this book is truly mind-blowing. The amount of data provided from the 3D reconstruction efforts can now be overlaid with the functional properties of identified cell types, resulting in a (synaptic) resolution previously deemed impossible. Given the number of different connectomic endeavors that are currently going on, we are very happy that Ian Meinertzhagen (Dalhousie University) agreed to discuss the future of Comparative Connectomics in his perspective piece. Going through the exciting chapters in this book, one wonders whether our limitation on genetic model organisms (worm, fruit fly, zebrafish, mouse) will disappear in the future? Recent progress in genome editing via Crispr/Cas9 could provide everyone with his or her model organism of choice in a relatively straightforward manner. This truly feels like the golden age for Neural Circuit Science. The possibilities seem limitless, and one can hardly wait to see where we will be taken next. In conclusion, we would like to thank all the contributing authors (many of them being up-and-coming junior Scientists), as well as the participants of the 2014 EMBO workshop, and our contacts at Springer for making this project possible. In theory, the speed at which the field of Neural Circuit Science progresses already seems to make it necessary to start planning a new follow-up book project, which would almost certainly look entirely different. But let us put first things first. For now, we look forward to more workshops, seminars, and meetings on this fundamental topic. The year 2014 and our peaceful gathering in Istanbul seems very far away right now in this rapidly changing world. We can only hope that the desire of people across the globe (Scientists and non-scientists alike) to come together and discuss on the basis of facts and data will prevail. In this particular case, we are proud to present the very tangible result of such interactions that we hope any interested reader will enjoy as much as we did: Decoding Neural Circuit Structure and Function (Cellular Dissection Using Genetic Model Organisms). Berlin, Germany January 2017 Arzu Çelik Mathias F. Wernet