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The role of ephrinA for retinotopic map formation in mouse visual cortex [Elektronische Ressource] : an optical imaging study / vorgelegt von Claire Creutzfeldt

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Aus dem Max-Planck-Institut für Neurobiologie, Abteilung Zelluläre und Systemneurobiologie Direktor: Prof. Tobias Bonhoeffer The role of EphrinA for retinotopic map formation in mouse visual cortex – an Optical Imaging study Dissertation zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Claire Creutzfeldt aus Göttingen 2003 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: Prof. Dr. med. U. Büttner Mitberichterstatter: Prof. Dr. Th. Heinzeller Prof. Dr. J. Herms Mitbetreuung durch die promovierten Mitarbeiter: Dr. Mark Hübener, Prof. Tobias Bonhoeffer Dekan: Prof. Dr. med. Dr. h.c. K. Peter Tag der mündlichen Prüfung: 27.November 2003 Acknowledgements Most of all, I want to thank Mark Hübener who faithfully and patiently supported me and helped me wherever he could. He taught me a great deal about imaging, about the visual cortex, and about science in general. Mark‘s enthusiasm and humour are very contagious and he stimulated my own thoughts and ideas and was great fun to work, discuss and laugh with. I am indebted to Sven Schütt who laid the foundations for this project. Thanks in particular to his computer programming skills, I could step into the experiments right away.

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Published 01 January 2003
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Aus dem Max-Planck-Institut für Neurobiologie, Abteilung Zelluläre und Systemneurobiologie Direktor: Prof. Tobias Bonhoeffer
The role of EphrinA for retinotopic map formation in mouse visual cortex  an Optical Imaging study Dissertation zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Claire Creutzfeldt aus Göttingen 2003
Mit Genehmigung der Medizinischen Fakultät der Universität München
Berichterstatter: Mitberichterstatter:Mitbetreuung durch die promovierten Mitarbeiter: Dr. Mark Hübener, Prof. Tobias Bonhoeffer Dekan: Prof. Dr. med. Dr. h.c. K. Peter Tag der mündlichen Prüfung: 27.November 2003
Prof. Dr. med. U. Büttner Prof. Dr. Th. Heinzeller Prof. Dr. J. Herms
Acknowledgements
Most of all, I want to thankMark Hübenerwho faithfully and patiently supported me and helped me wherever he could. He taught me a great deal about imaging, about the visual cortex, and about science in general. Marks enthusiasm and humour are very contagious and he stimulated my own thoughts and ideas and was great fun to work, discuss and laugh with. I am indebted toSven Schüttwho laid the foundations for this project. Thanks in particular to his computer programming skills, I could step into the experiments right away. The other essential originator of this project to whom I am very grateful, isLothar Lindemann,intriguing way of rendering mice deficient for allwho established this EphrinAs. I want to thankTobias Bonhoefferfor his advice on the project and for his help, both professional and personal, with the what next?. Many other lab members were of indispensable help, especiallyMax Sperlingwithout whom I would not have been able to work my way through Svens programmes, andMartin Kortefor his helpful and inspiring ideas and for proof reading the manuscript. All the members of the Bonhoeffer and Grothe labs together were responsible for a very pleasant and motivating atmosphere. I want to thankUlrich Büttnerfor reviewing this thesis. My mother,Mary,and my twin sister,Ruth,as well as my sisterCorinnaand brotherBenjamin,have been my most faithful and encouraging supporters throughout, just likeArmin,who accompanied me from the beginning of my thesis and helped me not only over this mountain.
to my father
The cortex is not a wishy-washy thing (Otto Creutzfeldt)
11.1 1.2 1.3 1.4 1.5 1.6 1.7 2 2.1 2.2 2.3 2.4 33.1 3.2 3.3 3.4 44.1 4.2
Contents
Introduction............................................................................................................3Mapsinthebrain.....................................................................................................3Gradients of molecular labels ..................................................................................4 Ephreceptorsandephrinligands........................................................................6Ephrin-A5 knockout mice........................................................................................8 Thalamocorticalmapping........................................................................................9In-vivofunctional imaging .......................................................................................9 Transgenic mice with a multiple ephrin-A deficiency...........................................10 Materials and Methods........................................................................................13 Surgery...................................................................................................................13Optical imaging......................................................................................................14 Analysis..................................................................................................................15 Genotyping.............................................................................................................17 Results ...................................................................................................................18Retinotopic organisation of the primary visual cortex...........................................19 Comparing maps in wild type and knockout mice.................................................20 Quantitative characteristics of retinotopic maps in wild type and knockout mice........................................................................................................................25 Retinotopic maps in young wild type and knockout mice.....................................29Discussion..............................................................................................................35The retinotopic map in the primary visual cortex of ephrin-A knockout mice is grossly normal........................................................................................................36 Adult ephrin-A knockout mice show a distortion in the map of the primary visualcortex...........................................................................................................39
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4.3 Mice lacking all ephrin-A ligands show a similar cortical phenotype as ephrin-A5knockoutmice..................................................................................................41
4.4 Young ephrin-A knockout mice exhibit a stronger phenotype than adult mice. ...45
4.5Conclusion.............................................................................................................46
Bibliography .....................................................................................................................48
Summary...........................................................................................................................53
Zusammenfassung (deutsch)...........................................................................................54
Curriculum Vitae .............................................................................................................56
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