[{"publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"month":"03","language":[{"iso":"eng"}],"doi":"10.1126/science.aav4837","project":[{"name":"Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex","call_identifier":"FP7","_id":"257A4776-B435-11E9-9278-68D0E5697425","grant_number":"281511"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000462738000034"]},"oa":1,"ec_funded":1,"file_date_updated":"2020-07-14T12:47:23Z","volume":363,"date_created":"2019-04-04T08:39:30Z","date_updated":"2024-03-28T23:30:16Z","related_material":{"record":[{"id":"6062","relation":"popular_science","status":"public"},{"id":"11932","relation":"dissertation_contains","status":"public"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/grid-cells-create-treasure-map-in-rat-brain/"}]},"author":[{"full_name":"Boccara, Charlotte N.","first_name":"Charlotte N.","last_name":"Boccara","id":"3FC06552-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7237-5109"},{"full_name":"Nardin, Michele","id":"30BD0376-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8849-6570","first_name":"Michele","last_name":"Nardin"},{"full_name":"Stella, Federico","first_name":"Federico","last_name":"Stella","id":"39AF1E74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9439-3148"},{"full_name":"O'Neill, Joseph","last_name":"O'Neill","first_name":"Joseph","id":"426376DC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","last_name":"Csicsvari"}],"publisher":"American Association for the Advancement of Science","department":[{"_id":"JoCs"}],"publication_status":"published","year":"2019","article_processing_charge":"No","has_accepted_license":"1","day":"29","scopus_import":"1","date_published":"2019-03-29T00:00:00Z","page":"1443-1447","article_type":"original","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","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.","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","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.","short":"C.N. Boccara, M. Nardin, F. Stella, J. O’Neill, J.L. Csicsvari, Science 363 (2019) 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.","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."},"publication":"Science","issue":"6434","abstract":[{"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.","lang":"eng"}],"type":"journal_article","file":[{"checksum":"5e6b16742cde10a560cfaf2130764da1","date_updated":"2020-07-14T12:47:23Z","date_created":"2020-05-14T09:11:10Z","file_id":"7826","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":9045923,"access_level":"open_access","file_name":"2019_Science_Boccara.pdf"}],"oa_version":"Submitted Version","intvolume":" 363","status":"public","title":"The entorhinal cognitive map is attracted to goals","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6194"},{"oa":1,"degree_awarded":"PhD","supervisor":[{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"language":[{"iso":"eng"}],"doi":"10.15479/at:ista:7132","month":"06","publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"HaJa"}],"year":"2019","date_updated":"2024-03-28T23:30:21Z","date_created":"2019-11-27T09:07:14Z","author":[{"id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87","first_name":"Catherine","last_name":"Mckenzie","full_name":"Mckenzie, Catherine"}],"related_material":{"record":[{"id":"6266","status":"public","relation":"old_edition"}]},"file_date_updated":"2020-07-14T12:47:50Z","page":"95","citation":{"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.","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.","ista":"Mckenzie C. 2019. Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria.","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","ieee":"C. Mckenzie, “Design and characterization of methods and biological components to realize synthetic neurotransmission,” Institute of Science and Technology Austria, 2019.","ama":"Mckenzie C. Design and characterization of methods and biological components to realize synthetic neurotransmission. 2019. doi:10.15479/at:ista:7132"},"date_published":"2019-06-27T00:00:00Z","day":"27","has_accepted_license":"1","article_processing_charge":"No","title":"Design and characterization of methods and biological components to realize synthetic neurotransmission","status":"public","ddc":["571","573"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7132","file":[{"checksum":"34d0fe0f6e0af97b5937205a3e350423","date_updated":"2020-07-14T12:47:50Z","date_created":"2019-11-27T09:06:10Z","relation":"source_file","file_id":"7133","file_size":5054633,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"dernst","access_level":"closed","file_name":"McKenzie PhD Thesis August 2018 - Corrected Final.docx"},{"file_size":3231837,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"McKenzie PhD Thesis August 2018 - Corrected Final.pdf","checksum":"140dfb5e3df7edca34f4b6fcc55d876f","date_created":"2019-11-27T09:06:10Z","date_updated":"2020-07-14T12:47:50Z","relation":"main_file","file_id":"7134"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"type":"dissertation","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."}]},{"file":[{"file_name":"2019_Hippocampus_Kaefer.pdf","access_level":"open_access","file_size":2132893,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"5950","date_created":"2019-02-11T10:42:51Z","date_updated":"2020-07-14T12:47:13Z","checksum":"5e8de271ca04aef92a5de42d6aac4404"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"5949","ddc":["570"],"title":"Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization","status":"public","intvolume":" 29","abstract":[{"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.","lang":"eng"}],"issue":"9","type":"journal_article","date_published":"2019-09-01T00:00:00Z","publication":"Hippocampus","citation":{"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.","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.","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","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.","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","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."},"article_type":"original","page":"802-816","day":"01","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","scopus_import":"1","author":[{"first_name":"Karola","last_name":"Käfer","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","full_name":"Käfer, Karola"},{"last_name":"Malagon-Vina","first_name":"Hugo","full_name":"Malagon-Vina, Hugo"},{"full_name":"Dickerson, Desiree","id":"444EB89E-F248-11E8-B48F-1D18A9856A87","last_name":"Dickerson","first_name":"Desiree"},{"full_name":"O'Neill, Joseph","first_name":"Joseph","last_name":"O'Neill"},{"full_name":"Trossbach, Svenja V.","last_name":"Trossbach","first_name":"Svenja V."},{"full_name":"Korth, Carsten","last_name":"Korth","first_name":"Carsten"},{"full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6825"}]},"date_updated":"2024-03-28T23:30:22Z","date_created":"2019-02-10T22:59:18Z","volume":29,"year":"2019","publication_status":"published","department":[{"_id":"JoCs"}],"publisher":"Wiley","file_date_updated":"2020-07-14T12:47:13Z","ec_funded":1,"doi":"10.1002/hipo.23076","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000480635400003"]},"isi":1,"quality_controlled":"1","project":[{"grant_number":"607616","_id":"257BBB4C-B435-11E9-9278-68D0E5697425","name":"Inter-and intracellular signalling in schizophrenia","call_identifier":"FP7"}],"month":"09"},{"publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"JoCs"}],"year":"2019","date_updated":"2023-09-07T13:01:42Z","date_created":"2019-08-21T15:00:57Z","author":[{"last_name":"Käfer","first_name":"Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","full_name":"Käfer, Karola"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"5949"}]},"file_date_updated":"2020-09-15T22:30:05Z","oa":1,"degree_awarded":"PhD","supervisor":[{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","last_name":"Csicsvari","full_name":"Csicsvari, Jozsef L"}],"language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:6825","month":"08","publication_identifier":{"issn":["2663-337X"]},"title":"The hippocampus and medial prefrontal cortex during flexible behavior","status":"public","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6825","file":[{"creator":"kkaefer","file_size":3205202,"content_type":"application/pdf","request_a_copy":0,"access_level":"open_access","file_name":"Thesis_Kaefer_PDFA.pdf","checksum":"2664420e332a33338568f4f3bfc59287","date_created":"2019-09-03T08:07:13Z","date_updated":"2020-09-06T22:30:03Z","embargo":"2020-09-05","file_id":"6846","relation":"main_file"},{"date_created":"2019-09-03T08:07:17Z","date_updated":"2020-09-15T22:30:05Z","checksum":"9a154eab6f07aa590a3d2651dc0d926a","relation":"main_file","file_id":"6847","file_size":2506835,"content_type":"application/zip","creator":"kkaefer","embargo_to":"open_access","file_name":"Thesis_Kaefer.zip","access_level":"closed"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"type":"dissertation","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. "}],"page":"89","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","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.","short":"K. Käfer, The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior, Institute of Science and Technology Austria, 2019.","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.","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."},"date_published":"2019-08-24T00:00:00Z","day":"24","article_processing_charge":"No","has_accepted_license":"1"},{"publication":"eLife","citation":{"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.","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).","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.","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.","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","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"},"date_published":"2019-06-06T00:00:00Z","scopus_import":"1","day":"06","has_accepted_license":"1","article_processing_charge":"No","_id":"6713","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice","ddc":["576"],"status":"public","intvolume":" 8","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:38Z","date_created":"2019-07-29T07:41:18Z","checksum":"fa0936fe58f0d9e3f8e75038570e5a17","relation":"main_file","file_id":"6721","file_size":6748249,"content_type":"application/pdf","creator":"apreinsp","file_name":"2019_eLife_Castro.pdf","access_level":"open_access"}],"type":"journal_article","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."}],"external_id":{"pmid":["31169497"],"isi":["000473588700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.7554/eLife.42014","language":[{"iso":"eng"}],"month":"06","year":"2019","pmid":1,"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"NiBa"}],"author":[{"last_name":"Castro","first_name":"João Pl","full_name":"Castro, João Pl"},{"first_name":"Michelle N.","last_name":"Yancoskie","full_name":"Yancoskie, Michelle N."},{"full_name":"Marchini, Marta","first_name":"Marta","last_name":"Marchini"},{"orcid":"0000-0002-9849-498X","id":"43FE426A-F248-11E8-B48F-1D18A9856A87","last_name":"Belohlavy","first_name":"Stefanie","full_name":"Belohlavy, Stefanie"},{"full_name":"Hiramatsu, Layla","last_name":"Hiramatsu","first_name":"Layla"},{"full_name":"Kučka, Marek","first_name":"Marek","last_name":"Kučka"},{"last_name":"Beluch","first_name":"William H.","full_name":"Beluch, William H."},{"last_name":"Naumann","first_name":"Ronald","full_name":"Naumann, Ronald"},{"last_name":"Skuplik","first_name":"Isabella","full_name":"Skuplik, Isabella"},{"last_name":"Cobb","first_name":"John","full_name":"Cobb, John"},{"full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton"},{"last_name":"Rolian","first_name":"Campbell","full_name":"Rolian, Campbell"},{"full_name":"Chan, Yingguang Frank","last_name":"Chan","first_name":"Yingguang Frank"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"9804"},{"status":"public","relation":"dissertation_contains","id":"11388"}]},"date_created":"2019-07-28T21:59:17Z","date_updated":"2024-03-28T23:30:23Z","volume":8,"article_number":"e42014","file_date_updated":"2020-07-14T12:47:38Z"},{"abstract":[{"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.","lang":"eng"}],"ec_funded":1,"article_number":"1910.05841","type":"preprint","date_updated":"2024-03-28T23:30:27Z","date_created":"2021-10-01T12:14:51Z","oa_version":"Preprint","author":[{"id":"340F461A-F248-11E8-B48F-1D18A9856A87","first_name":"Andrea C","last_name":"Hofmann","full_name":"Hofmann, Andrea C"},{"full_name":"Jirovec, Daniel","last_name":"Jirovec","first_name":"Daniel","orcid":"0000-0002-7197-4801","id":"4C473F58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Borovkov, Maxim","first_name":"Maxim","last_name":"Borovkov"},{"full_name":"Prieto Gonzalez, Ivan","first_name":"Ivan","last_name":"Prieto Gonzalez","id":"2A307FE2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5357"},{"full_name":"Ballabio, Andrea","first_name":"Andrea","last_name":"Ballabio"},{"full_name":"Frigerio, Jacopo","first_name":"Jacopo","last_name":"Frigerio"},{"full_name":"Chrastina, Daniel","first_name":"Daniel","last_name":"Chrastina"},{"first_name":"Giovanni","last_name":"Isella","full_name":"Isella, Giovanni"},{"id":"38DB5788-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8342-202X","first_name":"Georgios","last_name":"Katsaros","full_name":"Katsaros, Georgios"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"10058"}]},"status":"public","title":"Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits","publication_status":"submitted","department":[{"_id":"GeKa"}],"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.","_id":"10065","year":"2019","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"10","day":"13","article_processing_charge":"No","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"language":[{"iso":"eng"}],"date_published":"2019-10-13T00:00:00Z","doi":"10.48550/arXiv.1910.05841","project":[{"_id":"26A151DA-B435-11E9-9278-68D0E5697425","grant_number":"844511","name":"Majorana bound states in Ge/SiGe heterostructures","call_identifier":"H2020"},{"name":"Hole spin orbit qubits in Ge quantum wells","call_identifier":"FWF","_id":"2641CE5E-B435-11E9-9278-68D0E5697425","grant_number":"P30207"}],"publication":"arXiv","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","ieee":"A. C. Hofmann et al., “Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits,” arXiv. .","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","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.","short":"A.C. Hofmann, D. Jirovec, M. Borovkov, I. Prieto Gonzalez, A. Ballabio, J. Frigerio, D. Chrastina, G. Isella, G. Katsaros, ArXiv (n.d.).","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.","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."},"main_file_link":[{"url":"https://arxiv.org/abs/1910.05841","open_access":"1"}],"external_id":{"arxiv":["1910.05841"]},"oa":1},{"month":"03","publication_identifier":{"issn":["2050-084X"]},"acknowledged_ssus":[{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.7554/elife.41801","quality_controlled":"1","isi":1,"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"},{"call_identifier":"FWF","name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions","call_identifier":"FP7"},{"_id":"25388084-B435-11E9-9278-68D0E5697425","grant_number":"329540","name":"Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium","call_identifier":"FP7"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000462530200001"]},"oa":1,"file_date_updated":"2020-07-14T12:47:23Z","ec_funded":1,"article_number":"e41801","date_created":"2019-03-28T13:37:45Z","date_updated":"2024-03-28T23:30:30Z","volume":8,"author":[{"full_name":"Valosková, Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina","last_name":"Valosková"},{"first_name":"Julia","last_name":"Biebl","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Biebl, Julia"},{"full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","last_name":"Roblek","first_name":"Marko"},{"full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938","first_name":"Shamsi","last_name":"Emtenani"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"full_name":"Misova, Michaela","first_name":"Michaela","last_name":"Misova","id":"495A3C32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2427-6856"},{"first_name":"Aparna","last_name":"Ratheesh","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7190-0776","full_name":"Ratheesh, Aparna"},{"full_name":"Rodrigues, Patricia","first_name":"Patricia","last_name":"Rodrigues","id":"2CE4065A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Katerina","last_name":"Shkarina","full_name":"Shkarina, Katerina"},{"full_name":"Larsen, Ida Signe Bohse","last_name":"Larsen","first_name":"Ida Signe Bohse"},{"first_name":"Sergey Y","last_name":"Vakhrushev","full_name":"Vakhrushev, Sergey Y"},{"full_name":"Clausen, Henrik","last_name":"Clausen","first_name":"Henrik"},{"full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"id":"6530","relation":"dissertation_contains"},{"id":"8983","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"6546"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/"}]},"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"DaSi"}],"year":"2019","day":"26","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2019-03-26T00:00:00Z","publication":"eLife","citation":{"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.","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).","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.","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","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.","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"},"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."}],"type":"journal_article","oa_version":"Published Version","file":[{"file_name":"2019_eLife_Valoskova.pdf","access_level":"open_access","content_type":"application/pdf","file_size":4496017,"creator":"dernst","relation":"main_file","file_id":"6188","date_created":"2019-03-28T14:00:41Z","date_updated":"2020-07-14T12:47:23Z","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40"}],"title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","status":"public","ddc":["570"],"intvolume":" 8","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6187"},{"publication_identifier":{"issn":["2663-337X"]},"month":"06","project":[{"name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283"}],"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"supervisor":[{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E"}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:6546","file_date_updated":"2021-02-11T11:17:14Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"DaSi"}],"publication_status":"published","year":"2019","date_created":"2019-06-07T12:49:19Z","date_updated":"2023-09-19T10:15:54Z","related_material":{"record":[{"id":"6187","status":"public","relation":"part_of_dissertation"},{"id":"544","relation":"part_of_dissertation","status":"public"}]},"author":[{"full_name":"Valosková, Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina","last_name":"Valosková"}],"article_processing_charge":"No","has_accepted_license":"1","day":"07","page":"141","citation":{"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.","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.","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.","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","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.","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","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."},"date_published":"2019-06-07T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","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"}],"title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","ddc":["570"],"status":"public","_id":"6546","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"checksum":"68949c2d96210b45b981a23e9c9cd93c","date_updated":"2020-07-14T12:47:33Z","date_created":"2019-06-07T13:00:04Z","file_id":"6549","relation":"source_file","creator":"khribikova","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":14110626,"access_level":"closed","file_name":"Katarina Valoskova_PhD thesis_final version.docx","embargo_to":"open_access"},{"creator":"khribikova","file_size":10054156,"content_type":"application/pdf","file_name":"Katarina Valoskova_PhD thesis_final version.pdf","access_level":"open_access","date_updated":"2021-02-11T11:17:14Z","date_created":"2019-06-07T13:00:08Z","checksum":"555329cd76e196c96f5278c480ee2e6e","embargo":"2020-06-07","file_id":"6550","relation":"main_file"}],"oa_version":"Published Version"},{"date_published":"2019-04-30T00:00:00Z","citation":{"ama":"Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363","ista":"Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria.","ieee":"C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019.","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","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.","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."},"page":"140","day":"30","has_accepted_license":"1","article_processing_charge":"No","file":[{"file_size":13966891,"content_type":"application/pdf","creator":"cespinoza","file_name":"Espinozathesis_all2.pdf","access_level":"open_access","date_updated":"2021-02-11T11:17:15Z","date_created":"2019-05-07T16:00:39Z","checksum":"77c6c05cfe8b58c8abcf1b854375d084","relation":"main_file","file_id":"6389","embargo":"2020-05-09"},{"creator":"cespinoza","file_size":11159900,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Espinoza_Thesis.docx","embargo_to":"open_access","access_level":"closed","date_created":"2019-05-07T16:00:48Z","date_updated":"2020-07-14T12:47:28Z","checksum":"f6aa819f127691a2b0fc21c76eb09746","file_id":"6390","relation":"source_file"}],"oa_version":"Published Version","_id":"6363","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"status":"public","title":"Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits","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"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"doi":"10.15479/AT:ISTA:6363","supervisor":[{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"oa":1,"month":"04","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-000-8"]},"author":[{"id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4710-2082","first_name":"Claudia ","last_name":"Espinoza Martinez","full_name":"Espinoza Martinez, Claudia "}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"21"}]},"date_updated":"2023-09-15T12:03:48Z","date_created":"2019-04-30T11:56:10Z","year":"2019","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"PeJo"}],"file_date_updated":"2021-02-11T11:17:15Z"},{"date_published":"2019-10-01T00:00:00Z","citation":{"ama":"Huang M, Fu H, Chatterjee K, Goharshady AK. Modular verification for almost-sure termination of probabilistic programs. In: Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications . Vol 3. ACM; 2019. doi:10.1145/3360555","ista":"Huang M, Fu H, Chatterjee K, Goharshady AK. 2019. Modular verification for almost-sure termination of probabilistic programs. Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications . OOPSLA: Object-oriented Programming, Systems, Languages and Applications vol. 3, 129.","apa":"Huang, M., Fu, H., Chatterjee, K., & Goharshady, A. K. (2019). Modular verification for almost-sure termination of probabilistic programs. In Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications (Vol. 3). Athens, Greece: ACM. https://doi.org/10.1145/3360555","ieee":"M. Huang, H. Fu, K. Chatterjee, and A. K. Goharshady, “Modular verification for almost-sure termination of probabilistic programs,” in Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , Athens, Greece, 2019, vol. 3.","mla":"Huang, Mingzhang, et al. “Modular Verification for Almost-Sure Termination of Probabilistic Programs.” Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , vol. 3, 129, ACM, 2019, doi:10.1145/3360555.","short":"M. Huang, H. Fu, K. Chatterjee, A.K. Goharshady, in:, Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , ACM, 2019.","chicago":"Huang, Mingzhang, Hongfei Fu, Krishnendu Chatterjee, and Amir Kafshdar Goharshady. “Modular Verification for Almost-Sure Termination of Probabilistic Programs.” In Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , Vol. 3. ACM, 2019. https://doi.org/10.1145/3360555."},"publication":"Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications ","article_processing_charge":"No","has_accepted_license":"1","day":"01","oa_version":"Published Version","file":[{"checksum":"3482d8ace6fb4991eb7810e3b70f1b9f","date_created":"2019-08-12T15:40:57Z","date_updated":"2020-07-14T12:47:40Z","relation":"main_file","file_id":"6807","file_size":1024643,"content_type":"application/pdf","creator":"akafshda","access_level":"open_access","file_name":"oopsla-2019.pdf"},{"date_created":"2020-05-12T15:15:14Z","date_updated":"2020-07-14T12:47:40Z","checksum":"4e5a6fb2b59a75222a4e8335a5a60eac","file_id":"7821","relation":"main_file","creator":"dernst","file_size":538579,"content_type":"application/pdf","file_name":"2019_ACM_Huang.pdf","access_level":"open_access"}],"intvolume":" 3","ddc":["000"],"status":"public","title":"Modular verification for almost-sure termination of probabilistic programs","_id":"6780","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","abstract":[{"text":"In this work, we consider the almost-sure termination problem for probabilistic programs that asks whether a\r\ngiven probabilistic program terminates with probability 1. Scalable approaches for program analysis often\r\nrely on modularity as their theoretical basis. In non-probabilistic programs, the classical variant rule (V-rule)\r\nof Floyd-Hoare logic provides the foundation for modular analysis. Extension of this rule to almost-sure\r\ntermination of probabilistic programs is quite tricky, and a probabilistic variant was proposed in [16]. While the\r\nproposed probabilistic variant cautiously addresses the key issue of integrability, we show that the proposed\r\nmodular rule is still not sound for almost-sure termination of probabilistic programs.\r\nBesides establishing unsoundness of the previous rule, our contributions are as follows: First, we present a\r\nsound modular rule for almost-sure termination of probabilistic programs. Our approach is based on a novel\r\nnotion of descent supermartingales. Second, for algorithmic approaches, we consider descent supermartingales\r\nthat are linear and show that they can be synthesized in polynomial time. Finally, we present experimental\r\nresults on a variety of benchmarks and several natural examples that model various types of nested while\r\nloops in probabilistic programs and demonstrate that our approach is able to efficiently prove their almost-sure\r\ntermination property","lang":"eng"}],"type":"conference","language":[{"iso":"eng"}],"doi":"10.1145/3360555","conference":{"location":"Athens, Greece","start_date":"2019-10-23","end_date":"2019-10-25","name":"OOPSLA: Object-oriented Programming, Systems, Languages and Applications"},"project":[{"_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003","name":"Efficient Algorithms for Computer Aided Verification"},{"call_identifier":"FWF","name":"Game Theory","_id":"25863FF4-B435-11E9-9278-68D0E5697425","grant_number":"S11407"},{"call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications","_id":"2581B60A-B435-11E9-9278-68D0E5697425","grant_number":"279307"},{"_id":"267066CE-B435-11E9-9278-68D0E5697425","name":"Quantitative Analysis of Probablistic Systems with a focus on Crypto-currencies"},{"name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts","_id":"266EEEC0-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"external_id":{"arxiv":["1901.06087"]},"oa":1,"month":"10","volume":3,"date_created":"2019-08-09T09:54:20Z","date_updated":"2024-03-28T23:30:34Z","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8934"}]},"author":[{"last_name":"Huang","first_name":"Mingzhang","full_name":"Huang, Mingzhang"},{"last_name":"Fu","first_name":"Hongfei","full_name":"Fu, Hongfei"},{"full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","last_name":"Chatterjee","first_name":"Krishnendu"},{"id":"391365CE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1702-6584","first_name":"Amir Kafshdar","last_name":"Goharshady","full_name":"Goharshady, Amir Kafshdar"}],"department":[{"_id":"KrCh"}],"publisher":"ACM","publication_status":"published","year":"2019","license":"https://creativecommons.org/licenses/by-nc/4.0/","ec_funded":1,"file_date_updated":"2020-07-14T12:47:40Z","article_number":"129"}]