Holdings: Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression

Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression:

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Bibliographic Details
Main Author:	Wittgenstein, Julia von (Author)
Format:	Thesis Book
Language:	English
Published:	Erlangen ; Nürnberg [2018]
Subjects:	Hirnfunktion Genexpression Transkriptionsfaktor Gyrus dentatus Hochschulschrift
Online Access:	Inhaltsverzeichnis Inhaltsverzeichnis
Physical Description:	138 Seiten Illustrationen, Diagramme 21 cm

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MARC


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adam_text	CONTENT DANKSAGUNG............................................................................................................................................3 ABSTRACT....................................................................................................................................................5 ZUSAMMENFASSUNG............................................................................................................................... 7 FIGURES...................................................................................................................................................12 TABLES..................................................................................................................................................... 12 ABBREVIATIONS...................................................................................................................................... 13 INTRODUCTION..........................................................................................................................................17 I. FUNDAMENTAL ORGANIZATION OF MEMORY .................................................................................. 17 II. CELLULAR CORRELATES OF MEMORY STORAGE................................................................................. 18 I. SYNAPTIC PLASTICITY...................................................................................................................18 II. I NTRINSIC PLASTICITY....................................................................................................................20 III. MOLECULAR PATHWAYS UNDERLYING NEURONAL PLASTICITY........................................................22 I. POSTSYNAPTIC L T P ................................................................................................................. 22 II. PRESYNAPTIC LTP................................................................................................................... 24 III. INTRINSIC PLASTICITY.................................................................................................................. 25 IV. CYTOSKELETON AND SYNAPTIC PLASTICITY.................................................................................27 V. ACTIVITY-DEPENDENT GENE TRANSCRIPTION...............................................................................29 IV. THE HIPPOCAMPAL NETWORK AND REGION-SPECIFIC PLASTICITY .............................................. 32 V. THE FUNCTION OF SOX11 IN THE BRAIN.......................................................................................35 VI. AIM OF THE STUDY....................................................................................................................37 R ESULTS...................................................................................................................................................38 I. THE SOX11 LOCUS SHOWS TRAITS OF A TISSUE-SPECIFIC ACTIVITY-DEPENDENT GENE ................... 38 II. SOX11 IS INDUCED BY HIPPOCAMPAL ACTIVITY..........................................................................40 I. ECS TREATMENT ENHANCES SOX11 EXPRESSION IN THE D G .............................................. 41 II. EXPOSURE TO ENRICHED ENVIRONMENT INDUCES SOX11 IN MATURE DG GCS .................... 42 III. SOX11 IS EXPRESSED BY ACTIVATED DG GRANULE CELLS ...................................................... 45 IV. INDUCTION OF SOX11 IS REGION-SPECIFIC .............................................................................. 45 III. AAV-MEDIATED OVEREXPRESSION OF SOX11 EFFICIENTLY GENERATES A GAIN-OF-FUNCTION MODEL......................................................................................................................................... 47 I. AAV SEROTYPE 9 SHOWS EFFICIENT SPREADING FROM THE INJECTION SITE .............................. 47 II. AAV SEROTYPE 9 TARGETS PREFERENTIALLY MATURE NEURONAL CELLS ...................................... 48 III. AAV-MEDIATED OVEREXPRESSION OF SOX11 LEAVES EXPRESSION OF MOST DIFFERENTIATION STAGE-SPECIFIC MARKERS IN DG GRANULE CELLS INTACT..........................................................50 IV. THE ROLE OF SOX11 IN HIPPOCAMPUS-DEPENDENT LEARNING ............................................. 53 I. SOX11-OE DOES NOT IMPAIR THE FORMATION OF CONTEXT MEMORY ..................................... 53 II. SOX11-OE INCREASES STABILITY AGAINST INTERFERENCE WITH RECENT SPATIAL MEMORY ...... 56 V. SOX11 AS MODULATOR OF DG PLASTICITY....................................................................................59 I. SOX11-OE INCREASES EXCITABILITY OF DG GRANULE CELLS ................................................... 60 II. SOX11-OE INDUCES STRONGER INHIBITORY INPUT AND REDUCED SYNAPTIC PLASTICITY ON CIRCUIT LEVEL............................................................................................................................. 60 III. 80X11 EFFECTS ON DG PLASTICITY ARE INDEPENDENT FROM ADULT HIPPOCAMPAL NEUROGENESIS..........................................................................................................................65 VI. MOLECULAR MECHANISMS OF THE 80X11 EFFECTS ON DG PLASTICITY ................................... 67 I. SOX11-OE MODULATES GENES INVOLVED IN NEURONAL MEMBRANE CONDUCTANCE ........... 67 II. 8 0 X 1 1 -OE ALTERS EXPRESSION OF SEMAPHORIN SIGNALING NETWORKS AND CYTOSKELETAL COMPONENTS............................................................................................................................70 III. THE MICROTUBULE-REGULATORY PROTEIN STMN1 IS A TARGET GENE OF 8 0 X 1 1 .................... 73 IV. EXPRESSION OF PUTATIVE 80X11 TARGET GENES FOLLOWING STIMULATION BY A PHYSIOLOGICAL HIPPOCAMPAL STIMULUS...........................................................................................................76 VII. GENERATION AND VALIDATION OF A LOSS-OF-FUNCTION MOUSE MODEL TO INVESTIGATE THE ROLE OF 80X11 IN MATURE NEURONS...................................................................................................... 78 DISCUSSION............................................................................................................................................ 81 I. SOX11 IS AN ACTIVITY-DEPENDENT G EN E....................................................................................81 II. MOLECULAR MECHANISMS OF ACTIVITY-DEPENDENT SOX11 INDUCTION ........................................... 84 III. REGULATION OF REGION-SPECIFIC SOX11 EXPRESSION..............................................................86 IV. IDENTIFYING THE FUNCTION OF 80X11 IN MATURE DG NEURONS ............................................. 89 V. ACTIVITY-DEPENDENT SOX11 EXPRESSION AND DEPRESSIVE DISORDERS......................................93 MATERIALS AND METHODS...................................................................................................................... 95 I. MATERIALS..................................................................................................................................... 95 I. CHEMICALS AND REAGENTS....................................................................................................95 II. BUFFERS AND SOLUTIONS............................................................................................................96 III. ENZYMES AND BUFFERS FOR P C R S......................................................................................... 99 IV. ANTIBODIES.............................................................................................................................. 99 V. LIST OF PRIMERS AND EMSA OLIGONUCLEOTIDES .................................................................. 100 VI. VIRUSES..................................................................................................................................101 II. ANIMAL PROCEDURES..................................................................................................................101 I. ANIMAL HOUSING AND MOUSE LINES..................................................................................... 101 II. TAMOXIFEN TREATMENT..........................................................................................................103 III. ELECTROCONVULSIVE STIMULATION (ECS)............................................................................... 103 IV. ENRICHED ENVIRONMENT (EE) EXPLORATION ......................................................................... 104 V. STEREOTACTIC VIRUS INJECTIONS.............................................................................................. 104 VI. BRDU INJECTIONS.................................................................................................................... 104 VII. CONTEXTUAL FEAR CONDITIONING....................................................................................... 105 VIII. MORRIS WATER M A Z E .........................................................................................................106 III. ELECTROPHYSIOLOGY............................................................................................................... 107 IV. TISSUE PROCESSING AND ANALYSIS....................................................................................... 108 I. PERFUSION AND PREPARATION OF BRAIN SECTIONS...................................................................108 II. IMMUNOFLUORESCENCE STAINING...........................................................................................108 III. IMAGING AND COUNTING PROCEDURES .................................................................................. 108 IV. DISSECTION OF THE D G ..........................................................................................................109 V. RNA ISOLATION FROM DG TISSUE...........................................................................................109 VI. REVERSE TRANSCRIPTION PCR FOR CDNA SYNTHESIS ........................................................... 110 VII. REAL-TIME QUANTITATIVE PCR (QPCR) .......................................................................... 110 V. CELL CULTURE............................................................................................................................... 112 I. MAINTENANCE OF HEK293T CELLS....................................................................................... 112 II. TRANSFECTION OF HEK293T CELLS........................................................................................ 112 V I. ANALYSIS OF PROMOTER SEQUENCES.......................................................................................112 I. LUCIFERASE ASSAY..................................................................................................................112 II. ELECTROMOBILITY SHIFT ASSAY (EMSA)................................................................................ 113 VII. STATISTICS............................................................................................................................... 114 LITERATURE...................................................................................................................................115
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spelling	Wittgenstein, Julia von Verfasser (DE-588)116304282X aut Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression vorgelegt von Julia Freiin von Wittgenstein Erlangen ; Nürnberg [2018] 138 Seiten Illustrationen, Diagramme 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2018 Hirnfunktion (DE-588)4159930-5 gnd rswk-swf Genexpression (DE-588)4020136-3 gnd rswk-swf Transkriptionsfaktor (DE-588)4303350-7 gnd rswk-swf Gyrus dentatus (DE-588)4390857-3 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Transkriptionsfaktor (DE-588)4303350-7 s Gyrus dentatus (DE-588)4390857-3 s Genexpression (DE-588)4020136-3 s Hirnfunktion (DE-588)4159930-5 s DE-604 B:DE-101 application/pdf http://d-nb.info/1163042498/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030497865&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Wittgenstein, Julia von Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression Hirnfunktion (DE-588)4159930-5 gnd Genexpression (DE-588)4020136-3 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd Gyrus dentatus (DE-588)4390857-3 gnd
subject_GND	(DE-588)4159930-5 (DE-588)4020136-3 (DE-588)4303350-7 (DE-588)4390857-3 (DE-588)4113937-9
title	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression
title_auth	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression
title_exact_search	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression
title_full	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression vorgelegt von Julia Freiin von Wittgenstein
title_fullStr	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression vorgelegt von Julia Freiin von Wittgenstein
title_full_unstemmed	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression vorgelegt von Julia Freiin von Wittgenstein
title_short	Characterization of sox11 as a novel activity-dependent gene with dentate gyrus-specific expression
title_sort	characterization of sox11 as a novel activity dependent gene with dentate gyrus specific expression
topic	Hirnfunktion (DE-588)4159930-5 gnd Genexpression (DE-588)4020136-3 gnd Transkriptionsfaktor (DE-588)4303350-7 gnd Gyrus dentatus (DE-588)4390857-3 gnd
topic_facet	Hirnfunktion Genexpression Transkriptionsfaktor Gyrus dentatus Hochschulschrift
url	http://d-nb.info/1163042498/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030497865&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
work_keys_str_mv	AT wittgensteinjuliavon characterizationofsox11asanovelactivitydependentgenewithdentategyrusspecificexpression

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