Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus (Record no. 655797)

MARC details
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fixed length control field 04219ntm a22003497a 4500
003 - CONTROL NUMBER IDENTIFIER
control field AT-ISTA
005 - DATE AND TIME OF LATEST TRANSACTION
control field 20230705144003.0
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fixed length control field 230705s2022 au ||||| m||| 00| 0 eng d
040 ## - CATALOGING SOURCE
Transcribing agency ISTA
100 ## - MAIN ENTRY--PERSONAL NAME
Personal name Jevtic, Marijo
9 (RLIN) 972399
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Title Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus
260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT)
Name of publisher, distributor, etc. Institute of Science and Technology Austria
Date of publication, distribution, etc. 2022
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General note Thesis
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Formatted contents note Abstract
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Formatted contents note Acknowledgments
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Formatted contents note About the Author
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Formatted contents note List of Publications
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Formatted contents note Table of Contents
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Formatted contents note List of Figures
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Formatted contents note List of Tables
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Formatted contents note List of Abbreviations
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Formatted contents note 1 Introduction
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Formatted contents note 2 Materials and Methods
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Formatted contents note 3 Results
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Formatted contents note 4 Discussion
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Formatted contents note 5 Conclusions
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Formatted contents note References
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Formatted contents note A Appendix 1
520 ## - SUMMARY, ETC.
Summary, etc. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is implicated in complex processes such as learning and memory and various neurological diseases. These receptors are composed of different subunits and the subunit composition can affect channel properties, receptor trafficking and interaction with other associated proteins. Using the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for electron microscopy I investigated the number, density, and localization of AMPAR subunits, GluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse hippocampus. I have found that the immunogold labeling for all of these subunits in the postsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual increase from the pyramidal cell soma towards the distal part of stratum radiatum. The densities of extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities, while the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those for other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their densities were higher in the periphery than center of synapses. In contrast, the GluA3- containing receptors were more centrally localized compared to the GluA1- and GluA2- containing receptors. The hippocampus plays a central role in learning and memory. Contextual learning has been shown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus. However, proximodistal heterogeneity of this plasticity and particular contribution of different AMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an increase in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area. The intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred pattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but not stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings further contribute to our understanding of how specific hippocampal subregions and AMPA receptor subunits are involved in physiological learning. Although the immunolabeling results above shed light on subunit-specific plasticity in AMPAR distribution, no tools to visualize and study the subunit composition at the single channel level in situ have been available. Electron microscopy with conventional immunogold labeling approaches has limitations in the single channel analysis because of the large size of antibodies and steric hindrance hampering multiple subunit labeling of single channels. I managed to develop a new chemical labeling system using a short peptide tag and small synthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to proteins of interest (reactive tag system). I additionally made substantial progress into adapting this system for AMPA receptor subunits.
856 ## - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="https://doi.org/10.15479/at:ista:11393">https://doi.org/10.15479/at:ista:11393</a>
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  Not Lost Dewey Decimal Classification     Library Library 05/07/2023   Quiet Room AT-ISTA#002828 15/09/2025 05/07/2023 Book

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