Animal Models of Epilepsy: Methods and Innovations PDF
Preview Animal Models of Epilepsy: Methods and Innovations
NE U R OM E T H O D S Series Editor Wolfgang Walz University of Saskatchewan Saskatoon, SK, Canada For other titles published in this series, go to www.springer.com/series/7657 NE U R OM E T H O D S Animal Models of Epilepsy Methods and Innovations Edited by Scott C. Baraban Ph.D. University of California, San Francisco, CA, USA Editor Scott C. Baraban Department of Neurological Surgery Box 0520 University of California, San Francisco 513 Parnassus Avenue San Francisco, CA 94143 USA Preface to the Series Under the guidance of its founders Alan Boulton and Glen Baker, the Neuromethods series by Humana Press has been very successful since the first volume appeared in 1985. In about 17 years, 37 volumes have been published. In 2006, Springer Science + Business Media made a renewed commitment to this series. The new program will focus on methods that are either unique to the nervous system and excitable cells or which need special consideration to be applied to the neurosciences. The program will strike a balance between recent and exciting developments like those concerning new animal models of disease, imaging, in vivo methods, and more established techniques. These include immunocytochemistry and electrophysiological technologies. New trainees in neurosciences still need a sound footing in these older methods in order to apply a critical approach to their results. The careful application of methods is probably the most important step in the process of scientific inquiry. In the past, new methodologies led the way in developing new disciplines in the biological and medical sciences. For example, Physiology emerged out of Anatomy in the 19th century by harnessing new methods based on the newly discovered phenomenon of electricity. Nowadays, the relationships between disciplines and methods are more complex. Methods are now widely shared between disciplines and research areas. New developments in electronic publishing also make it possible for scientists to download chapters or protocols selectively within a very short time of encountering them. This new approach has been taken into account in the design of individual volumes and chapters in this series. Wolfgang Walz v Preface Epilepsy is fairly unique among the various neurological disorders as it provides the neuroscientist with almost boundless opportunities to examine basic neurobiological mechanisms. Not surprisingly, advances in epilepsy research are closely tied to devel- opment of innovative neurobiological methodologies. In many cases the practical application of these innovations – especially in the context of a neurological disorder with anatomical, molecular, electrophysiological, and behavioral components such as epilepsy – can be found in the development of new animal models. In turn, our understanding of the pathogenesis of epilepsy (and new therapy development) greatly benefits from these models. Taking advantage of transgenic and homologous recom- bination techniques, laboratories have recently moved beyond the standard convulsant or stimulation models in rat to develop novel mouse models of epilepsy. This forward thinking approach has recently been applied to genetically tractable ‘‘simple’’ species such as Drosophila melanogaster (fruit flies), Caenorhabditis elegans (worms), Xenopus laevis (tadpoles), and Danio rerio (zebrafish). With contributions from prominent investigators in this field, this book provides a review of these emerging animal models of epilepsy. Prior textbooks devoted to models of seizure and epilepsy almost exclusively categorized rat models with little attention paid to these more innovative approaches. Here we attempt to diverge from the conventional epilepsy literature and focus on animal models that attempt to incorporate the latest technological advancements in neurobiology. While some of these models and approaches are, admittedly, at very early stages of development and may ultimately fall short of widespread utilization, it is through the consideration and presentation of these models that the authors’ hope to advance and challenge the field of epilepsy research. Here we also attempt to move beyond a strict review of animal models and also include innovative approaches to epilepsy research that are just now appearing in the literature. These range from modeling seizure activity in silica to advanced strategies for seizure detection and gene therapy. These latter innovations are important as some may lead to better therapeutic treatments for patients suffering from intractable forms of epilepsy. As a Neuromethods book, our overall objective is to provide an accessible and thought-provoking review of recent advancements in epilepsy research. Contributing authors encompass a wide spectrum of expertise from basic neurobiology, through sophisticated electrophysiology and genetics, to practicing epilepsy clinicians. Authors were carefully selected who not only offer a broad perspective on epilepsy, but, in each case, have pioneered the innovative approaches described in this book. Scott C. Baraban vii Contents Preface to the Series . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Color Plates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii 1. The Nematode, Caenorhabditis elegans, as an Emerging Model for Investigating Epilepsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Cody J. Locke, Kim A. Caldwell, and Guy A. Caldwell 2. The Genetics and Molecular Biology of Seizure Susceptibility in Drosophila . . . . . 27 Juan Song and Mark A. Tanouye 3. The Albino Xenopus laevis Tadpole as a Novel Model of Developmental Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 D. Sesath Hewapathirane and Kurt Haas 4. Zebrafish as a Simple Vertebrate Organism for Epilepsy Research . . . . . . . . . . . . . 59 Scott C. Baraban 5. Modeling Tuberous Sclerosis Complex: Brain Development and Hyperexcitability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Kevin C. Ess 6. BK Potassium Channel Mutations Affecting Neuronal Function and Epilepsy . . . . 87 David Petrik, Qing H. Chen, and Robert Brenner 7. Mouse Models of Benign Familial Neonatal Convulsions (BFNC): Mutations in KCNQ (Kv7) Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Nanda A. Singh, James F. Otto, Mark F. Leppert, H. Steve White, and Karen S. Wilcox 8. Interneuron Loss as a Cause of Seizures: Lessons from Interneuron-Deficient Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Dorothy Jones-Davis, Maria-Elisa Calcagnotto, and Joy Y. Sebe 9. Imaging Seizure Propagation In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Andrew J. Trevelyan and Rafael Yuste 10. Complexity Untangled: Large-Scale Realistic Computational Models in Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Robert J. Morgan and Ivan Soltesz 11. Organotypic Hippocampal Slice Cultures as a Model of Limbic Epileptogenesis . . 183 Suzanne B. Bausch 12. Seizure Analysis and Detection In Vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Javier Echauz, Stephen Wong, and Brian Litt 13. Viral Vector Gene Therapy for Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Stacey B. Foti, Shelley J. Russek, Amy R. Brooks-Kayal, and Thomas J. McCown ix x Contents 14. Neural Stem Cells in Experimental Mesial Temporal Lobe Epilepsy . . . . . . . . . . . . 251 Michelle M. Kron and Jack M. Parent Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265 Contributors SCOTT C. BARABAN • Department of Neurological Surgery, University of California, San Francisco, CA, USA SUZANNE B. BAUSCH • Department of Pharmacology and Graduate Program in Neuroscience, Uniformed Services University, Bethesda, MD, USA ROBERT BRENNER • Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA AMY R. BROOKS-KAYAL • Division of Neurology, Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia, Philadelphia, PA, USA MARIA ELISA CALCAGNOTTO • Department of Physiology, Universidade Federal de Sa˜o Paulo - UNIFESP, Sa˜o Paulo, Brazil GUY A. CALDWELL • Departments of Biological Sciences, Neurology and Neuroscience, Center for Neurodegeneration and Experimental Therapeutics, University of Ala- bama at Birmingham, Birmingham, AL, USA KIM A. CALDWELL • Departments of Biological Sciences, Neurology and Neuroscience, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA QING H. CHEN • Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA JAVIER ECHAUZ, J.E. • Research, Atlanta, GA, USA KEVIN C. ESS • Departments of Neurology and Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN, USA STACEY B. FOTI • Program in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA KURT HAAS • Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada D. SESATH HEWAPATHIRANE • Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada DOROTHY JONES-DAVIS • Department of Neurological Surgery, University of California, San Francisco, CA, USA MICHELLE M. KRON • Department of Neurology, University of Michigan, Ann Arbor, MI, USA MARK F. LEPPERT • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA BRIAN LITT • Departments of Neurology and Bioengineering, University of Pennsylvania, Philadelphia, PA, USA CODY J. LOCKE • Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA THOMAS J. MCOWN • University of North Carolina Gene Therapy Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA xi xii Contributors ROBERT J. MORGAN • Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA JAMES F. OTTO • Anticonvulsant Drug Development Program, University of Utah, Salt Lake City, UT, USA JACK M. PARENT • Department of Neurology, University of Michigan, Ann Arbor, MI, USA DAVID PETRIK • Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA SHELLEY J. RUSSEK • Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA JOY Y. SEBE • Department of Neurological Surgery, University of California, San Francisco, CA, USA NANDA A. SINGH • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA IVAN SOLTESZ • Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA JUAN SONG • Departments of Environmental Sciences, Policy and Management, Division of Organisms and Environment, Molecular and Cellular Biology, Division of Neurobiology, University of California, Berkeley, Berkeley, CA, USA MARK A. TANOUYE • Departments of Environmental Sciences, Policy and Management, Division of Organisms and Environment, Molecular and Cellular Biology, Division of Neurobiology, University of California, Berkeley, Berkeley, CA, USA ANDREW J. TREVELYAN • Institute of Neuroscience, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK H. STEVE WHITE • Anticonvulsant Drug Development Program, University of Utah, Salt Lake City, UT, USA KAREN WILCOX • Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA STEPHEN WONG • Departments of Neurology and Bioengineering, University of Pennsylvania, Philadelphia, PA, USA RAFAEL YUSTE • HHMI, Department of Biological Sciences, Columbia University, New York, NY, USA Color Plates Color Plate 1 In vivo imaging of dendritic arbor growth and synapse formation in X. laevis tadpoles. (A) Single-cell electroporation allowing tar- geted neuronal labeling and transfection in vivo. Scale bar ¼ 2 mm. (Chapter 3, Fig. 4; see discussion on p. 53 and complete caption on p. 54) Color Plate 2 Tsc1 morphant zebrafish. (Anatomy) Histological analysis of con- trol and tsc1a morphants. Immunostaining with the neuronal marker HuC/HuD of control-injected (A) and tsc1a morphant (B) larvae, and semi-thin plastic sections of control-injected (C,E,G,I) and tsc1a morphant (D,F,H,J) larvae are shown. (Chapter 4, Fig. 3; see discus- sion on p. 69 and complete caption on p. 70) Synapsin Color Plate 3 Confocal images of brain sections from Tsc1 CKO mice immu- nostained for SMI311 (red, neuronal marker) and phospho-S6 (green). This staining reveals large, dysplastic appearing neurons from white matter (A) or the cortex (B). (Chapter 5, Fig. 4; see discussion on p. 81) Color Plate 4 Diagram of BK channel a (pore-forming) subunit and accessory b subunits. Annotations indicate relevant functional domains and sites containing epilepsy mutations (3 delA750 and gain-of- function mutation D434G for subunit). (Chapter 6, Fig. 1; see discussion on p. 88) Color Plate 5 BK and b4 effect on action potential waveform in dentate gyrus granule cells. Action potential was selected from 10th spike during a 300 pA current injection. Average data are plotted at right. Red trace is4 knockout, blue trace is wild type plus SK channel blocker UCL1684, black trace is wild type. (Chapter 6, Fig. 3; see discussion on p. 97) Color Plate 6 Cortical interneuron loss in selected GABAergic interneuron- deficient mice. Wild-type mice display normal connectivity in the cortex. (Chapter 8, Fig. 3; see discussion on p. 134 and complete caption on p. 135) 2+ Color Plate 7 Somatic Ca transients reveal episodic localized recruitment. (A) 2+ The derivation of the cellular Ca signal. (Chapter 9, Fig. 4; see discussion on p. 156 and complete caption on p. 157) xiii
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