NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice:
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1. Verfasser: | |
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Format: | Abschlussarbeit Buch |
Sprache: | English |
Veröffentlicht: |
2004
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Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | 101 Bl. Ill., graph. Darst. 30 cm |
Internformat
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Datensatz im Suchindex
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adam_text | Content
1. Introduction __ _1
1.1 Preface. 1
1.2 Signal transmission in the central nervous system 1
1.3 Excitatory and inhibitory synaptic transmission 2
1.4 Ionotropic glutamate receptors 3
1.4.1 Classification of ionotropic glutamate receptors 3
1.4.2 Structure of ionotropic glutamate receptors 4
1.4.3 The Q/R/N site of ionotropic glutamate receptors 5
1.4.4 Subunit stoichiometry 5
1.5 The NMDA receptor 5
1.5.1 Role of the NMDAR during synaptic transmission 5
1.5.2 Modulation and pharmacology of NMDAR channel function 6
1.5.3 NMDAR subunit diversity 6
1.5.4 The C terminal tail of the NMDAR 7
1.5.5 Developmental profile of NMDAR subunits and effect on kinetics 7
1.5.6 NMDAR subunits and synaptic plasticity 8
1.5.7 NMDARs and disease 8
1.6 The hippocampus 9
1.7 Long term potentiation 10
1.7.1 LTP: an overview 10
1.7.2 LTP at the Schaffer collateral CA 1 synapse 10
1.7.2.1 The role of Car* in LTP at the Schaffer collateral CA 1 synapse 10
1.7.2.2 Ca:+ sensors involved in LTP induction 12
1.7.2.3 Pre or postsynaptic locus of LTP expression? 13
1.7.2.4 LTP induction protocols 15
1.8 The aim of this study 17
1.8.1 Difficulties in previous studies to locate the Ca:+ source for LTP induction 17
1.8.2 Approach of this study to locate the Ca2+ source for LTP induction 18
2. Results 22
2.1. NR1(R) and NR2A(S) expression in HEK293 cells 22
2.1.1 Current voltage relationships indicate the effect of NR1 (R) and NR2A(S) on Mg2+ block and on
Ca2+ permeability of NMDAR channels 22
2.1.2 NR1(R) and NR2A(S) affect the kinetics of NMDAR mediated currents 23
2.1.3 NR1(R) has no effect on glycine potency but slightly increases glutamate potency 25
2.2 Phenotype of mice expressing NR1(R) or NR2A(S) 27
2.2.1 Temporal and spatial restriction of NR1(R) expression in mice 27
2.2.2 NR2A(S) expression in NR2AS/S mice and NR2A expression in wild type mice are endogenously
restricted to distinct brain areas during development 29
2.3 Electrophysiological characterization of NRl+/Rneo/TgCre4 and NR2AS/S mice 30
2.3.1 Consequences of NR1(R) or NR2A(S) expression in CA1 neurons for block of NMDARs by Mg2+ _ 30
2.3.2 Kinetics of NMDAR mediated currents in NRl+/Rnei7TgCre4 mice 33
2.3.3 Reduced AMPAR mediated transmission in CA 1 neurons of NRl+/Rneo/TgCre4 mice 37
2.3.4 Whole cell LTP induced by low frequency stimulation in NRl+/RneoArgCre4 mice 41
2.3.5 Whole cell LTP induced by low frequency stimulation in NR2AS/S mice 44
2.3.6 Whole cell LTP induced by high frequency stimulation in NRl+/Rnc7TgCrc4 mice 45
2.3.7 Whole cell HFS LTP in the presence of different concentrations of intracellular Ca2+ buffers 47
2.3.8 Field LTP induced by HFS in NRl+ Rneo/TgCre4 mice 49
3. Discussion 57
3.1 NR1(R)/NR2A channels in HEK293 cells not only show Ca2+ impermeability and
abolished Mg2* block, but also lower peak currents at 60 mV 51
3.2 NR1(R) prolongs the kinetics of NMDAR mediated currents 53
3.3 A Cre loxP system restricts NR1(R) expression to postnatal stages and to forebrain 55
3.4 Reduced postsynaptic AMPAR mediated response in CA1 neurons of NRl+/Rneo/TgCre4
mice 58
3.5 Ca2+ signaling during LTP induction: progress and limitations 63
3.6 Ca2+ sources involved in LFS and HFS LTP 64
3.7 The impaired Mg2+ block of NMDARs is not responsible for failure to induce LTP by
LFS in NRl+/Rne7TgCre4 mice 66
3.8 LTP can be induced by HFS in NRl+/Rne7TgCre4 mice 68
3.9 Concluding remarks 71
4. Materials and Methods 73
4.1 Mouse genotyping____ 73
4.2 Slice preparation_ 73
4.3 Cre immnnostaining 74
4.4 Cell culture 75
4.5 Electrophysiology 75
4.5.1 The patch clamp technique 75
4.5.2 The patch clamp setup 75
4.5.3 Whole cell recording in HEK293 cells 76
4.5.4 Synaptic current recordings 76
4.5.5 Somatic current recordings 77
4.5.6 Whole cell LTP 77
4.5.7 Field LTP 77
4.5.8 Data acquisition and analysis 78
5. Abbreviations 80
6. References 84
7. Publications 101
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author | Pawlak, Verena |
author_facet | Pawlak, Verena |
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building | Verbundindex |
bvnumber | BV019709766 |
ctrlnum | (OCoLC)254210098 (DE-599)BVBBV019709766 |
discipline | Medizin |
format | Thesis Book |
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indexdate | 2024-07-09T20:04:21Z |
institution | BVB |
language | English |
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spelling | Pawlak, Verena Verfasser aut NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice [von Verena Pawlak] 2004 101 Bl. Ill., graph. Darst. 30 cm txt rdacontent n rdamedia nc rdacarrier Heidelberg, Univ., Diss., 2004. Enth. Zsfassung in engl. und dt. Sprache Langzeitpotenzierung (DE-588)4738763-4 gnd rswk-swf Calciumion (DE-588)4147181-7 gnd rswk-swf NMDA-Rezeptor (DE-588)4264187-1 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content NMDA-Rezeptor (DE-588)4264187-1 s Calciumion (DE-588)4147181-7 s Langzeitpotenzierung (DE-588)4738763-4 s DE-604 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=013037155&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Pawlak, Verena NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice Langzeitpotenzierung (DE-588)4738763-4 gnd Calciumion (DE-588)4147181-7 gnd NMDA-Rezeptor (DE-588)4264187-1 gnd |
subject_GND | (DE-588)4738763-4 (DE-588)4147181-7 (DE-588)4264187-1 (DE-588)4113937-9 |
title | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice |
title_auth | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice |
title_exact_search | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice |
title_full | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice [von Verena Pawlak] |
title_fullStr | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice [von Verena Pawlak] |
title_full_unstemmed | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice [von Verena Pawlak] |
title_short | NMDA receptors with reduced Ca2+ permeability and their effect on hippocampal long-term potentiation in mutant mice |
title_sort | nmda receptors with reduced ca2 permeability and their effect on hippocampal long term potentiation in mutant mice |
topic | Langzeitpotenzierung (DE-588)4738763-4 gnd Calciumion (DE-588)4147181-7 gnd NMDA-Rezeptor (DE-588)4264187-1 gnd |
topic_facet | Langzeitpotenzierung Calciumion NMDA-Rezeptor Hochschulschrift |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=013037155&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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