University of Groningen. Molecular mechanisms of synaptic plasticity Nijholt, Ingrid
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1 University of Groningen Molecular mechanisms of synaptic plasticity Nijholt, Ingrid IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2002 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Nijholt, I. M. (2002). Molecular mechanisms of synaptic plasticity: implications for immediate early gene expression and learning Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:
2 MOLECULAR MECHANISMS OF SYNAPTIC PLASTICITY Implications for immediate early gene expression and learning
3 Die Deutsche Bibliothek CIP-Einheitsaufnahme Nijholt, Ingrid Maria: Molecular mechanisms of synaptic plasticity: Implications for immediate early gene expression and learning / door Ingrid Maria Nijholt. 1. Aufl. Göttingen : Cuvillier, 2002 Zugl.: Groningen, Univ., Diss., 2002 ISBN The research described in this thesis was carried out at the Max Planck Institute for Experimental Medicine in the Department of Molecular Neuroendocrinology, Göttingen, Germany. The author was a Ph.D. student at the Graduate School for Behavioral and Cognitive Neurosciences of the University of Groningen, the Netherlands. CUVILLIER VERLAG, Göttingen, 2002 Nonnenstieg 8, Göttingen Telefon: Telefax: Alle Rechte vorbehalten. Ohne ausdrückliche Genehmigung des Verlages ist es nicht gestattet, das Buch oder Teile daraus auf fotomechanischem Weg (Fotokopie, Mikrokopie) zu vielfältigen. 1. Auflage, 2002 Gedruckt auf säurefreiem Papier ISBN
4 RIJKSUNIVERSITEIT GRONINGEN MOLECULAR MECHANISMS OF SYNAPTIC PLASTICITY Implications for immediate early gene expression and learning PROEFSCHRIFT ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op maandag 7 oktober 2002 om uur door INGRID MARIA NIJHOLT geboren op 19 juni 1973 te Drachten
5 Promotores: Referent: Prof. dr. J. M. Koolhaas Prof. dr. J. Spiess Dr. T. Blank Beoordelingscommissie: Prof. dr. P.G.M. Luiten Prof. dr. M. Joëls Prof. dr. H.W.G.M. Boddeke ISBN
6 Mit Steinen, die einem in den Weg gelegt werden, kann man auch was schönes bauen.
7 CONTENTS Chapter 1: General introduction 1 1. Synaptic plasticity Basic principles of synaptic transmission Second messenger pathways Protein kinases Protein phosphatases Phosphoproteins Glutamate receptors NMDA receptor 7 2. Synaptic plasticity and gene expression CREB FOS Synaptic plasticity and learning and memory Hippocampus Long-term potentiation and depression as a model for learning 12 and memory 3.3 Influence of stress on synaptic plasticity and learning and memory Corticotropin-releasing factor as mediator of the stress 15 response Chapter 2: Modulation of hypothalamic NMDA receptor function by cyclic 33 AMP-dependent protein kinase and phosphatases Chapter 3: The phosphoprotein DARPP-32 mediates camp-dependent 45 potentiation of striatal N-methyl-D-aspartate responses Chapter 4: In vivo NMDA/dopamine interaction resulting in FOS production 62 in the limbic system and basal ganglia of the mouse brain. Chapter 5: In vivo CREB phosphorylation mediated by dopamine and NMDA 79 receptor activation in mouse hippocampus and caudate nucleus. Chapter 6: The corticotropin-releasing factor receptor 1 antagonist CP-154, markedly enhances associative learning and paired- pulse facilitation immediately after a stressful experience. Chapter 7: Priming of long-term potentiation in mouse hippocampus by 101 corticotropin-releasing factor and acute stress: implications for hippocampus-dependent learning. page
8 Chapter 8: Modulation of neuronal excitability and associative learning by 117 different corticotropin-releasing factor-signaling cascades in mouse hippocampus Chapter 9: Summary and general discussion Brain regional differences in the modulation of the NMDA 135 receptors by phosphorylation events 1.1 DARPP Possible physiological relevance of PKA-mediated NMDA receptor 138 modulation in the hypothalamus 1.3 Direct versus indirect phosphorylation of the NMDA receptor Brain regional differences in gene expression Specificity in signaling pathways Synaptic plasticity and learning and memory Metaplasticity Correlation between synaptic plasticity and learning Possible role of calcium/calmodulin-dependent protein 147 kinase II Comparison between two mouse inbred strains Balb/c and 148 C57BL/6N 4. Concluding remarks 149 Nederlandse samenvatting 159 Supplement: NS-257, a novel competitive AMPA receptor antagonist, 165 interacts with kainate and NMDA receptors. List of publications 179 Dankwoord 183 Curriculum vitae 185
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