{"publisher":"Institute of Science and Technology Austria","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_created":"2021-06-17T14:10:47Z","oa":1,"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"related_material":{"record":[{"status":"public","id":"9756","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"9437"},{"id":"8532","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","id":"612","status":"public"}]},"status":"public","title":"2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning","date_updated":"2023-09-11T12:55:53Z","month":"06","article_processing_charge":"No","supervisor":[{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444"}],"day":"01","degree_awarded":"PhD","file":[{"file_id":"9563","file_size":77299142,"date_created":"2021-06-17T14:03:14Z","date_updated":"2022-07-02T22:30:04Z","content_type":"application/pdf","creator":"dkleindienst","access_level":"open_access","embargo":"2022-07-01","file_name":"Thesis.pdf","checksum":"659df5518db495f679cb1df9e9bd1d94","relation":"main_file"},{"date_updated":"2022-07-02T22:30:04Z","file_id":"9564","file_size":369804895,"date_created":"2021-06-17T14:04:30Z","checksum":"3bcf63a2b19e5b6663be051bea332748","relation":"source_file","content_type":"application/zip","creator":"dkleindienst","access_level":"closed","embargo_to":"open_access","file_name":"Thesis_source.zip"}],"type":"dissertation","abstract":[{"text":"Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry.","lang":"eng"}],"department":[{"_id":"GradSch"},{"_id":"RySh"}],"date_published":"2021-06-01T00:00:00Z","publication_status":"published","acknowledged_ssus":[{"_id":"EM-Fac"}],"year":"2021","ddc":["570"],"file_date_updated":"2022-07-02T22:30:04Z","publication_identifier":{"issn":["2663-337X"]},"doi":"10.15479/at:ista:9562","page":"124","author":[{"first_name":"David","last_name":"Kleindienst","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"_id":"9562","citation":{"mla":"Kleindienst, David. <i>2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:9562\">10.15479/at:ista:9562</a>.","ieee":"D. Kleindienst, “2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning,” Institute of Science and Technology Austria, 2021.","ista":"Kleindienst D. 2021. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. Institute of Science and Technology Austria.","apa":"Kleindienst, D. (2021). <i>2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:9562\">https://doi.org/10.15479/at:ista:9562</a>","chicago":"Kleindienst, David. “2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:9562\">https://doi.org/10.15479/at:ista:9562</a>.","ama":"Kleindienst D. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:9562\">10.15479/at:ista:9562</a>","short":"D. Kleindienst, 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning, Institute of Science and Technology Austria, 2021."}}