--- _id: '6848' abstract: - lang: eng text: Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9. acknowledged_ssus: - _id: ScienComp acknowledgement: " We thank R. Thompson, G. Effantin and V.-V. Hodirnau for their assistance with collecting NADP+, NADPH and apo datasets, respectively. Data processing was performed at the IST high-performance computing cluster.\r\nThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement no. 665385." article_processing_charge: No article_type: letter_note author: - first_name: Domen full_name: Kampjut, Domen id: 37233050-F248-11E8-B48F-1D18A9856A87 last_name: Kampjut - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 citation: ama: Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 2019;573(7773):291–295. doi:10.1038/s41586-019-1519-2 apa: Kampjut, D., & Sazanov, L. A. (2019). Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1519-2 chicago: Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1519-2. ieee: D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating transhydrogenase,” Nature, vol. 573, no. 7773. Springer Nature, pp. 291–295, 2019. ista: Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 573(7773), 291–295. mla: Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature, vol. 573, no. 7773, Springer Nature, 2019, pp. 291–295, doi:10.1038/s41586-019-1519-2. short: D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295. date_created: 2019-09-04T06:21:41Z date_published: 2019-09-12T00:00:00Z date_updated: 2024-03-27T23:30:14Z day: '12' ddc: - '572' department: - _id: LeSa doi: 10.1038/s41586-019-1519-2 ec_funded: 1 external_id: isi: - '000485415400061' pmid: - '31462775' file: - access_level: open_access checksum: 52728cda5210a3e9b74cc204e8aed3d5 content_type: application/pdf creator: lsazanov date_created: 2020-11-26T16:33:44Z date_updated: 2020-11-26T16:33:44Z file_id: '8821' file_name: Manuscript_final_acc_withFigs_SI_opt_red.pdf file_size: 3066206 relation: main_file success: 1 file_date_updated: 2020-11-26T16:33:44Z has_accepted_license: '1' intvolume: ' 573' isi: 1 issue: '7773' language: - iso: eng month: '09' oa: 1 oa_version: Submitted Version page: 291–295 pmid: 1 project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Nature publication_identifier: eissn: - 1476-4687 issn: - 0028-0836 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Website relation: press_release url: https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/ record: - id: '8340' relation: dissertation_contains status: public scopus_import: '1' status: public title: Structure and mechanism of mitochondrial proton-translocating transhydrogenase type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 573 year: '2019' ... --- _id: '6194' abstract: - lang: eng text: Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space. article_processing_charge: No article_type: original author: - first_name: Charlotte N. full_name: Boccara, Charlotte N. id: 3FC06552-F248-11E8-B48F-1D18A9856A87 last_name: Boccara orcid: 0000-0001-7237-5109 - first_name: Michele full_name: Nardin, Michele id: 30BD0376-F248-11E8-B48F-1D18A9856A87 last_name: Nardin orcid: 0000-0001-8849-6570 - first_name: Federico full_name: Stella, Federico id: 39AF1E74-F248-11E8-B48F-1D18A9856A87 last_name: Stella orcid: 0000-0001-9439-3148 - first_name: Joseph full_name: O'Neill, Joseph id: 426376DC-F248-11E8-B48F-1D18A9856A87 last_name: O'Neill - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 citation: ama: Boccara CN, Nardin M, Stella F, O’Neill J, Csicsvari JL. The entorhinal cognitive map is attracted to goals. Science. 2019;363(6434):1443-1447. doi:10.1126/science.aav4837 apa: Boccara, C. N., Nardin, M., Stella, F., O’Neill, J., & Csicsvari, J. L. (2019). The entorhinal cognitive map is attracted to goals. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aav4837 chicago: Boccara, Charlotte N., Michele Nardin, Federico Stella, Joseph O’Neill, and Jozsef L Csicsvari. “The Entorhinal Cognitive Map Is Attracted to Goals.” Science. American Association for the Advancement of Science, 2019. https://doi.org/10.1126/science.aav4837. ieee: C. N. Boccara, M. Nardin, F. Stella, J. O’Neill, and J. L. Csicsvari, “The entorhinal cognitive map is attracted to goals,” Science, vol. 363, no. 6434. American Association for the Advancement of Science, pp. 1443–1447, 2019. ista: Boccara CN, Nardin M, Stella F, O’Neill J, Csicsvari JL. 2019. The entorhinal cognitive map is attracted to goals. Science. 363(6434), 1443–1447. mla: Boccara, Charlotte N., et al. “The Entorhinal Cognitive Map Is Attracted to Goals.” Science, vol. 363, no. 6434, American Association for the Advancement of Science, 2019, pp. 1443–47, doi:10.1126/science.aav4837. short: C.N. Boccara, M. Nardin, F. Stella, J. O’Neill, J.L. Csicsvari, Science 363 (2019) 1443–1447. date_created: 2019-04-04T08:39:30Z date_published: 2019-03-29T00:00:00Z date_updated: 2024-03-27T23:30:16Z day: '29' ddc: - '570' department: - _id: JoCs doi: 10.1126/science.aav4837 ec_funded: 1 external_id: isi: - '000462738000034' file: - access_level: open_access checksum: 5e6b16742cde10a560cfaf2130764da1 content_type: application/pdf creator: dernst date_created: 2020-05-14T09:11:10Z date_updated: 2020-07-14T12:47:23Z file_id: '7826' file_name: 2019_Science_Boccara.pdf file_size: 9045923 relation: main_file file_date_updated: 2020-07-14T12:47:23Z has_accepted_license: '1' intvolume: ' 363' isi: 1 issue: '6434' language: - iso: eng month: '03' oa: 1 oa_version: Submitted Version page: 1443-1447 project: - _id: 257A4776-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281511' name: Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Science publication_identifier: eissn: - 1095-9203 issn: - 0036-8075 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/grid-cells-create-treasure-map-in-rat-brain/ record: - id: '6062' relation: popular_science status: public - id: '11932' relation: dissertation_contains status: public scopus_import: '1' status: public title: The entorhinal cognitive map is attracted to goals type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 363 year: '2019' ... --- _id: '7132' abstract: - lang: eng text: "A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta.\r\nSynthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Catherine full_name: Mckenzie, Catherine id: 3EEDE19A-F248-11E8-B48F-1D18A9856A87 last_name: Mckenzie citation: ama: Mckenzie C. Design and characterization of methods and biological components to realize synthetic neurotransmission. 2019. doi:10.15479/at:ista:7132 apa: Mckenzie, C. (2019). Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:7132 chicago: Mckenzie, Catherine. “Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:7132. ieee: C. Mckenzie, “Design and characterization of methods and biological components to realize synthetic neurotransmission,” Institute of Science and Technology Austria, 2019. ista: Mckenzie C. 2019. Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria. mla: Mckenzie, Catherine. Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:7132. short: C. Mckenzie, Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission, Institute of Science and Technology Austria, 2019. date_created: 2019-11-27T09:07:14Z date_published: 2019-06-27T00:00:00Z date_updated: 2024-03-27T23:30:21Z day: '27' ddc: - '571' - '573' degree_awarded: PhD department: - _id: HaJa doi: 10.15479/at:ista:7132 file: - access_level: closed checksum: 34d0fe0f6e0af97b5937205a3e350423 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-11-27T09:06:10Z date_updated: 2020-07-14T12:47:50Z file_id: '7133' file_name: McKenzie PhD Thesis August 2018 - Corrected Final.docx file_size: 5054633 relation: source_file - access_level: open_access checksum: 140dfb5e3df7edca34f4b6fcc55d876f content_type: application/pdf creator: dernst date_created: 2019-11-27T09:06:10Z date_updated: 2020-07-14T12:47:50Z file_id: '7134' file_name: McKenzie PhD Thesis August 2018 - Corrected Final.pdf file_size: 3231837 relation: main_file file_date_updated: 2020-07-14T12:47:50Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '95' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6266' relation: old_edition status: public status: public supervisor: - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 title: Design and characterization of methods and biological components to realize synthetic neurotransmission type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '5949' abstract: - lang: eng text: Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Karola full_name: Käfer, Karola id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87 last_name: Käfer - first_name: Hugo full_name: Malagon-Vina, Hugo last_name: Malagon-Vina - first_name: Desiree full_name: Dickerson, Desiree id: 444EB89E-F248-11E8-B48F-1D18A9856A87 last_name: Dickerson - first_name: Joseph full_name: O'Neill, Joseph last_name: O'Neill - first_name: Svenja V. full_name: Trossbach, Svenja V. last_name: Trossbach - first_name: Carsten full_name: Korth, Carsten last_name: Korth - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 citation: ama: Käfer K, Malagon-Vina H, Dickerson D, et al. Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. 2019;29(9):802-816. doi:10.1002/hipo.23076 apa: Käfer, K., Malagon-Vina, H., Dickerson, D., O’Neill, J., Trossbach, S. V., Korth, C., & Csicsvari, J. L. (2019). Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. Wiley. https://doi.org/10.1002/hipo.23076 chicago: Käfer, Karola, Hugo Malagon-Vina, Desiree Dickerson, Joseph O’Neill, Svenja V. Trossbach, Carsten Korth, and Jozsef L Csicsvari. “Disrupted-in-Schizophrenia 1 Overexpression Disrupts Hippocampal Coding and Oscillatory Synchronization.” Hippocampus. Wiley, 2019. https://doi.org/10.1002/hipo.23076. ieee: K. Käfer et al., “Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization,” Hippocampus, vol. 29, no. 9. Wiley, pp. 802–816, 2019. ista: Käfer K, Malagon-Vina H, Dickerson D, O’Neill J, Trossbach SV, Korth C, Csicsvari JL. 2019. Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. 29(9), 802–816. mla: Käfer, Karola, et al. “Disrupted-in-Schizophrenia 1 Overexpression Disrupts Hippocampal Coding and Oscillatory Synchronization.” Hippocampus, vol. 29, no. 9, Wiley, 2019, pp. 802–16, doi:10.1002/hipo.23076. short: K. Käfer, H. Malagon-Vina, D. Dickerson, J. O’Neill, S.V. Trossbach, C. Korth, J.L. Csicsvari, Hippocampus 29 (2019) 802–816. date_created: 2019-02-10T22:59:18Z date_published: 2019-09-01T00:00:00Z date_updated: 2024-03-27T23:30:22Z day: '01' ddc: - '570' department: - _id: JoCs doi: 10.1002/hipo.23076 ec_funded: 1 external_id: isi: - '000480635400003' file: - access_level: open_access checksum: 5e8de271ca04aef92a5de42d6aac4404 content_type: application/pdf creator: dernst date_created: 2019-02-11T10:42:51Z date_updated: 2020-07-14T12:47:13Z file_id: '5950' file_name: 2019_Hippocampus_Kaefer.pdf file_size: 2132893 relation: main_file file_date_updated: 2020-07-14T12:47:13Z has_accepted_license: '1' intvolume: ' 29' isi: 1 issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 802-816 project: - _id: 257BBB4C-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '607616' name: Inter-and intracellular signalling in schizophrenia publication: Hippocampus publication_status: published publisher: Wiley quality_controlled: '1' related_material: record: - id: '6825' relation: dissertation_contains status: public scopus_import: '1' status: public title: Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 29 year: '2019' ... --- _id: '6825' abstract: - lang: eng text: "The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions.\r\nWith tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay.\r\nWe found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by\r\nmaze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between\r\ncell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC\r\ntrajectory-replay at the goal positively correlated with rule-switching performance. \r\nFinally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Karola full_name: Käfer, Karola id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87 last_name: Käfer citation: ama: Käfer K. The hippocampus and medial prefrontal cortex during flexible behavior. 2019. doi:10.15479/AT:ISTA:6825 apa: Käfer, K. (2019). The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6825 chicago: Käfer, Karola. “The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6825. ieee: K. Käfer, “The hippocampus and medial prefrontal cortex during flexible behavior,” Institute of Science and Technology Austria, 2019. ista: Käfer K. 2019. The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria. mla: Käfer, Karola. The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6825. short: K. Käfer, The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior, Institute of Science and Technology Austria, 2019. date_created: 2019-08-21T15:00:57Z date_published: 2019-08-24T00:00:00Z date_updated: 2023-09-07T13:01:42Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: JoCs doi: 10.15479/AT:ISTA:6825 file: - access_level: open_access checksum: 2664420e332a33338568f4f3bfc59287 content_type: application/pdf creator: kkaefer date_created: 2019-09-03T08:07:13Z date_updated: 2020-09-06T22:30:03Z embargo: 2020-09-05 file_id: '6846' file_name: Thesis_Kaefer_PDFA.pdf file_size: 3205202 relation: main_file request_a_copy: 0 - access_level: closed checksum: 9a154eab6f07aa590a3d2651dc0d926a content_type: application/zip creator: kkaefer date_created: 2019-09-03T08:07:17Z date_updated: 2020-09-15T22:30:05Z embargo_to: open_access file_id: '6847' file_name: Thesis_Kaefer.zip file_size: 2506835 relation: main_file file_date_updated: 2020-09-15T22:30:05Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '89' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '5949' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 title: The hippocampus and medial prefrontal cortex during flexible behavior type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6713' abstract: - lang: eng text: Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response. article_number: e42014 article_processing_charge: No author: - first_name: João Pl full_name: Castro, João Pl last_name: Castro - first_name: Michelle N. full_name: Yancoskie, Michelle N. last_name: Yancoskie - first_name: Marta full_name: Marchini, Marta last_name: Marchini - first_name: Stefanie full_name: Belohlavy, Stefanie id: 43FE426A-F248-11E8-B48F-1D18A9856A87 last_name: Belohlavy orcid: 0000-0002-9849-498X - first_name: Layla full_name: Hiramatsu, Layla last_name: Hiramatsu - first_name: Marek full_name: Kučka, Marek last_name: Kučka - first_name: William H. full_name: Beluch, William H. last_name: Beluch - first_name: Ronald full_name: Naumann, Ronald last_name: Naumann - first_name: Isabella full_name: Skuplik, Isabella last_name: Skuplik - first_name: John full_name: Cobb, John last_name: Cobb - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Campbell full_name: Rolian, Campbell last_name: Rolian - first_name: Yingguang Frank full_name: Chan, Yingguang Frank last_name: Chan citation: ama: Castro JP, Yancoskie MN, Marchini M, et al. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 2019;8. doi:10.7554/eLife.42014 apa: Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L., Kučka, M., … Chan, Y. F. (2019). An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42014 chicago: Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42014. ieee: J. P. Castro et al., “An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 8, e42014. mla: Castro, João Pl, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife, vol. 8, e42014, eLife Sciences Publications, 2019, doi:10.7554/eLife.42014. short: J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M. Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F. Chan, ELife 8 (2019). date_created: 2019-07-28T21:59:17Z date_published: 2019-06-06T00:00:00Z date_updated: 2024-03-27T23:30:22Z day: '06' ddc: - '576' department: - _id: NiBa doi: 10.7554/eLife.42014 external_id: isi: - '000473588700001' pmid: - '31169497' file: - access_level: open_access checksum: fa0936fe58f0d9e3f8e75038570e5a17 content_type: application/pdf creator: apreinsp date_created: 2019-07-29T07:41:18Z date_updated: 2020-07-14T12:47:38Z file_id: '6721' file_name: 2019_eLife_Castro.pdf file_size: 6748249 relation: main_file file_date_updated: 2020-07-14T12:47:38Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '9804' relation: research_data status: public - id: '11388' relation: dissertation_contains status: public scopus_import: '1' status: public title: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ... --- _id: '10065' abstract: - lang: eng text: We study double quantum dots in a Ge/SiGe heterostructure and test their maturity towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability, from two single quantum dots to a double quantum dot. We measure Pauli spin blockade and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for sensing charge transitions in the double quantum dot at interest. In conclusion, Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit. acknowledged_ssus: - _id: M-Shop - _id: NanoFab acknowledgement: "We thank Matthias Brauns for helpful discussions and careful proofreading of the manuscript. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844511 and from the FWF project P30207. The research was supported by the Scientific Service Units of IST Austria through resources provided by the MIBA machine shop and the nanofabrication\r\nfacility." article_number: '1910.05841' article_processing_charge: No author: - first_name: Andrea C full_name: Hofmann, Andrea C id: 340F461A-F248-11E8-B48F-1D18A9856A87 last_name: Hofmann - first_name: Daniel full_name: Jirovec, Daniel id: 4C473F58-F248-11E8-B48F-1D18A9856A87 last_name: Jirovec orcid: 0000-0002-7197-4801 - first_name: Maxim full_name: Borovkov, Maxim last_name: Borovkov - first_name: Ivan full_name: Prieto Gonzalez, Ivan id: 2A307FE2-F248-11E8-B48F-1D18A9856A87 last_name: Prieto Gonzalez orcid: 0000-0002-7370-5357 - first_name: Andrea full_name: Ballabio, Andrea last_name: Ballabio - first_name: Jacopo full_name: Frigerio, Jacopo last_name: Frigerio - first_name: Daniel full_name: Chrastina, Daniel last_name: Chrastina - first_name: Giovanni full_name: Isella, Giovanni last_name: Isella - first_name: Georgios full_name: Katsaros, Georgios id: 38DB5788-F248-11E8-B48F-1D18A9856A87 last_name: Katsaros orcid: 0000-0001-8342-202X citation: ama: Hofmann AC, Jirovec D, Borovkov M, et al. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. doi:10.48550/arXiv.1910.05841 apa: Hofmann, A. C., Jirovec, D., Borovkov, M., Prieto Gonzalez, I., Ballabio, A., Frigerio, J., … Katsaros, G. (n.d.). Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. https://doi.org/10.48550/arXiv.1910.05841 chicago: Hofmann, Andrea C, Daniel Jirovec, Maxim Borovkov, Ivan Prieto Gonzalez, Andrea Ballabio, Jacopo Frigerio, Daniel Chrastina, Giovanni Isella, and Georgios Katsaros. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, n.d. https://doi.org/10.48550/arXiv.1910.05841. ieee: A. C. Hofmann et al., “Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits,” arXiv. . ista: Hofmann AC, Jirovec D, Borovkov M, Prieto Gonzalez I, Ballabio A, Frigerio J, Chrastina D, Isella G, Katsaros G. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv, 1910.05841. mla: Hofmann, Andrea C., et al. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, 1910.05841, doi:10.48550/arXiv.1910.05841. short: A.C. Hofmann, D. Jirovec, M. Borovkov, I. Prieto Gonzalez, A. Ballabio, J. Frigerio, D. Chrastina, G. Isella, G. Katsaros, ArXiv (n.d.). date_created: 2021-10-01T12:14:51Z date_published: 2019-10-13T00:00:00Z date_updated: 2024-03-27T23:30:26Z day: '13' department: - _id: GeKa doi: 10.48550/arXiv.1910.05841 ec_funded: 1 external_id: arxiv: - '1910.05841' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1910.05841 month: '10' oa: 1 oa_version: Preprint project: - _id: 26A151DA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '844511' name: Majorana bound states in Ge/SiGe heterostructures - _id: 2641CE5E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P30207 name: Hole spin orbit qubits in Ge quantum wells publication: arXiv publication_status: submitted related_material: record: - id: '10058' relation: dissertation_contains status: public status: public title: Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2019' ... --- _id: '6187' abstract: - lang: eng text: Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis. acknowledged_ssus: - _id: LifeSc article_number: e41801 article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková - first_name: Julia full_name: Biebl, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Biebl - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Michaela full_name: Misova, Michaela id: 495A3C32-F248-11E8-B48F-1D18A9856A87 last_name: Misova orcid: 0000-0003-2427-6856 - first_name: Aparna full_name: Ratheesh, Aparna id: 2F064CFE-F248-11E8-B48F-1D18A9856A87 last_name: Ratheesh orcid: 0000-0001-7190-0776 - first_name: Patricia full_name: Rodrigues, Patricia id: 2CE4065A-F248-11E8-B48F-1D18A9856A87 last_name: Rodrigues - first_name: Katerina full_name: Shkarina, Katerina last_name: Shkarina - first_name: Ida Signe Bohse full_name: Larsen, Ida Signe Bohse last_name: Larsen - first_name: Sergey Y full_name: Vakhrushev, Sergey Y last_name: Vakhrushev - first_name: Henrik full_name: Clausen, Henrik last_name: Clausen - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: ama: Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 2019;8. doi:10.7554/elife.41801 apa: Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.41801 chicago: Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801. ieee: K. Valosková et al., “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801. mla: Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife, vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801. short: K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019). date_created: 2019-03-28T13:37:45Z date_published: 2019-03-26T00:00:00Z date_updated: 2024-03-27T23:30:29Z day: '26' ddc: - '570' department: - _id: DaSi doi: 10.7554/elife.41801 ec_funded: 1 external_id: isi: - '000462530200001' file: - access_level: open_access checksum: cc0d1a512559d52e7e7cb0e9b9854b40 content_type: application/pdf creator: dernst date_created: 2019-03-28T14:00:41Z date_updated: 2020-07-14T12:47:23Z file_id: '6188' file_name: 2019_eLife_Valoskova.pdf file_size: 4496017 relation: main_file file_date_updated: 2020-07-14T12:47:23Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 253CDE40-B435-11E9-9278-68D0E5697425 grant_number: '24283' name: Examination of the role of a MFS transporter in the migration of Drosophila immune cells - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: The role of Drosophila TNF alpha in immune cell invasion - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 25388084-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '329540' name: 'Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/ record: - id: '6530' relation: dissertation_contains - id: '8983' relation: dissertation_contains status: public - id: '6546' relation: dissertation_contains status: public scopus_import: '1' status: public title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ... --- _id: '6546' abstract: - lang: eng text: "Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n" acknowledged_ssus: - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková citation: ama: Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546 apa: Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546 chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546. ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019. ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. mla: Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546. short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-06-07T12:49:19Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-19T10:15:54Z day: '07' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:6546 file: - access_level: closed checksum: 68949c2d96210b45b981a23e9c9cd93c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: khribikova date_created: 2019-06-07T13:00:04Z date_updated: 2020-07-14T12:47:33Z embargo_to: open_access file_id: '6549' file_name: Katarina Valoskova_PhD thesis_final version.docx file_size: 14110626 relation: source_file - access_level: open_access checksum: 555329cd76e196c96f5278c480ee2e6e content_type: application/pdf creator: khribikova date_created: 2019-06-07T13:00:08Z date_updated: 2021-02-11T11:17:14Z embargo: 2020-06-07 file_id: '6550' file_name: Katarina Valoskova_PhD thesis_final version.pdf file_size: 10054156 relation: main_file file_date_updated: 2021-02-11T11:17:14Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '141' project: - _id: 253CDE40-B435-11E9-9278-68D0E5697425 grant_number: '24283' name: Examination of the role of a MFS transporter in the migration of Drosophila immune cells publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6187' relation: part_of_dissertation status: public - id: '544' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6363' abstract: - lang: eng text: "Distinguishing between similar experiences is achieved by the brain \ in a process called pattern separation. In the hippocampus, pattern \ separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into \ non-overlapping output firing patterns. Winners-take-all (WTA) mechanism \ is a theoretical model for pattern separation in which a \"winner\" \ cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not \ itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined \ but less abundant than PV+interneurons–GC connectivity, leading to an \ asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. \ This process relied on lateral inhibition, fast-signaling properties of \ PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate \ gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 citation: ama: Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363 apa: Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363 chicago: Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363. ieee: C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019. ista: Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. mla: Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363. short: C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019. date_created: 2019-04-30T11:56:10Z date_published: 2019-04-30T00:00:00Z date_updated: 2023-09-15T12:03:48Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:6363 file: - access_level: open_access checksum: 77c6c05cfe8b58c8abcf1b854375d084 content_type: application/pdf creator: cespinoza date_created: 2019-05-07T16:00:39Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-05-09 file_id: '6389' file_name: Espinozathesis_all2.pdf file_size: 13966891 relation: main_file - access_level: closed checksum: f6aa819f127691a2b0fc21c76eb09746 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cespinoza date_created: 2019-05-07T16:00:48Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6390' file_name: Espinoza_Thesis.docx file_size: 11159900 relation: source_file file_date_updated: 2021-02-11T11:17:15Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '140' publication_identifier: isbn: - 978-3-99078-000-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '21' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ...