[{"publication_status":"published","publication_identifier":{"issn":["10974199"]},"intvolume":"       101","abstract":[{"lang":"eng","text":"Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next."}],"volume":101,"date_created":"2019-01-13T22:59:10Z","article_type":"original","day":"02","scopus_import":"1","author":[{"first_name":"Haibing","last_name":"Xu","full_name":"Xu, Haibing","id":"310349D0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter","last_name":"Baracskay","full_name":"Baracskay, Peter","id":"361CC00E-F248-11E8-B48F-1D18A9856A87"},{"id":"426376DC-F248-11E8-B48F-1D18A9856A87","full_name":"O'Neill, Joseph","last_name":"O'Neill","first_name":"Joseph"},{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari","orcid":"0000-0002-5193-4036","first_name":"Jozsef L"}],"title":"Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze","oa_version":"Published Version","citation":{"short":"H. Xu, P. Baracskay, J. O’Neill, J.L. Csicsvari, Neuron 101 (2019) 119–132.e4.","ieee":"H. Xu, P. Baracskay, J. O’Neill, and J. L. Csicsvari, “Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze,” <i>Neuron</i>, vol. 101, no. 1. Elsevier, p. 119–132.e4, 2019.","ama":"Xu H, Baracskay P, O’Neill J, Csicsvari JL. Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze. <i>Neuron</i>. 2019;101(1):119-132.e4. doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.11.015\">10.1016/j.neuron.2018.11.015</a>","mla":"Xu, Haibing, et al. “Assembly Responses of Hippocampal CA1 Place Cells Predict Learned Behavior in Goal-Directed Spatial Tasks on the Radial Eight-Arm Maze.” <i>Neuron</i>, vol. 101, no. 1, Elsevier, 2019, p. 119–132.e4, doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.11.015\">10.1016/j.neuron.2018.11.015</a>.","apa":"Xu, H., Baracskay, P., O’Neill, J., &#38; Csicsvari, J. L. (2019). Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2018.11.015\">https://doi.org/10.1016/j.neuron.2018.11.015</a>","chicago":"Xu, Haibing, Peter Baracskay, Joseph O’Neill, and Jozsef L Csicsvari. “Assembly Responses of Hippocampal CA1 Place Cells Predict Learned Behavior in Goal-Directed Spatial Tasks on the Radial Eight-Arm Maze.” <i>Neuron</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.neuron.2018.11.015\">https://doi.org/10.1016/j.neuron.2018.11.015</a>.","ista":"Xu H, Baracskay P, O’Neill J, Csicsvari JL. 2019. Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze. Neuron. 101(1), 119–132.e4."},"issue":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"JoCs"}],"month":"01","main_file_link":[{"open_access":"1","url":"https://www.doi.org/10.1016/j.neuron.2018.11.015"}],"quality_controlled":"1","page":"119-132.e4","_id":"5828","date_updated":"2023-09-07T12:06:37Z","type":"journal_article","article_processing_charge":"No","doi":"10.1016/j.neuron.2018.11.015","publisher":"Elsevier","ec_funded":1,"date_published":"2019-01-02T00:00:00Z","publication":"Neuron","status":"public","project":[{"_id":"257A4776-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex","grant_number":"281511"}],"year":"2019","isi":1,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"837"}],"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/reading-rats-minds/"}]},"external_id":{"isi":["000454791500014"]}},{"date_created":"2018-12-11T11:48:46Z","day":"23","author":[{"last_name":"Xu","full_name":"Xu, Haibing","id":"310349D0-F248-11E8-B48F-1D18A9856A87","first_name":"Haibing"}],"title":"Reactivation of the hippocampal cognitive map in goal-directed spatial tasks","oa_version":"Published Version","file_date_updated":"2020-07-14T12:48:12Z","publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","has_accepted_license":"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision. ","lang":"eng"}],"department":[{"_id":"JoCs"}],"file":[{"creator":"dernst","date_updated":"2020-07-14T12:48:12Z","file_size":3589490,"date_created":"2019-04-05T08:59:51Z","file_id":"6213","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","file_name":"2017_Xu_Haibing_Thesis_Source.docx","checksum":"f11925fbbce31e495124b6bc4f10573c","relation":"source_file"},{"creator":"dernst","date_updated":"2020-07-14T12:48:12Z","date_created":"2019-04-05T08:59:51Z","file_size":11668613,"file_id":"6214","content_type":"application/pdf","access_level":"open_access","file_name":"2017_Xu_Thesis_IST.pdf","checksum":"ffb10749a537d615fab1ef0937ccb157","relation":"main_file"}],"supervisor":[{"orcid":"0000-0002-5193-4036","first_name":"Jozsef L","last_name":"Csicsvari","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L"}],"month":"08","citation":{"chicago":"Xu, Haibing. “Reactivation of the Hippocampal Cognitive Map in Goal-Directed Spatial Tasks.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:th_858\">https://doi.org/10.15479/AT:ISTA:th_858</a>.","ista":"Xu H. 2017. Reactivation of the hippocampal cognitive map in goal-directed spatial tasks. Institute of Science and Technology Austria.","mla":"Xu, Haibing. <i>Reactivation of the Hippocampal Cognitive Map in Goal-Directed Spatial Tasks</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_858\">10.15479/AT:ISTA:th_858</a>.","apa":"Xu, H. (2017). <i>Reactivation of the hippocampal cognitive map in goal-directed spatial tasks</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_858\">https://doi.org/10.15479/AT:ISTA:th_858</a>","ama":"Xu H. Reactivation of the hippocampal cognitive map in goal-directed spatial tasks. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_858\">10.15479/AT:ISTA:th_858</a>","short":"H. Xu, Reactivation of the Hippocampal Cognitive Map in Goal-Directed Spatial Tasks, Institute of Science and Technology Austria, 2017.","ieee":"H. Xu, “Reactivation of the hippocampal cognitive map in goal-directed spatial tasks,” Institute of Science and Technology Austria, 2017."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"language":[{"iso":"eng"}],"pubrep_id":"858","_id":"837","date_updated":"2023-09-07T12:06:38Z","type":"dissertation","alternative_title":["ISTA Thesis"],"article_processing_charge":"No","doi":"10.15479/AT:ISTA:th_858","publisher":"Institute of Science and Technology Austria","page":"93","ddc":["571"],"publist_id":"6811","year":"2017","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"5828"}]},"acknowledgement":"I am very grateful for the opportunity I have had as a graduate student to explore and incredibly interesting branch of neuroscience, and for the people who made it possible. Firstly, I would like to offer my thanks to my supervisor Professor Jozsef Csicsvari for his great support, guidance and patience offered over the years. The door to his office was always open whenever I had questions. I have learned a lot from him about carefully designing experiments, asking interesting questions and how to integrate results into a broader picture. I also express my gratitude to the remarkable post- doc , Dr. Joseph O’Neill. He is a gre at scientific role model who is always willing to teach , and advice and talk through problems with his full attention. Many thanks to my wonderful “office mates” over the years and their support and encouragement, Alice Avernhe, Philipp Schönenberger, Desiree Dickerson, Karel Blahna, Charlotte Boccara, Igor Gridchyn, Peter Baracskay, Krisztián Kovács, Dámaris Rangel, Karola Käfer and Federico Stella. They were the ones in the lab for the many useful discussions about science and for making the laboratory such a nice and friendly place to work in. A special thank goes to Michael LoBianco and Jago Wallenschus for wonderful technical support. I would also like to thank Professor Peter Jonas and Professor David M Bannerman for being my qualifying exam and thesi s committee members despite their busy schedule. I am also very thankful to IST Austria for their support all throughout my PhD. ","date_published":"2017-08-23T00:00:00Z","degree_awarded":"PhD","status":"public"},{"extern":"1","publication":"Nature Medicine","status":"public","language":[{"iso":"eng"}],"date_published":"2010-11-21T00:00:00Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","issue":"12","pmid":1,"citation":{"short":"L. Zhou, F. Li, H. Xu, C. Luo, H. Wu, M. Zhu, W. Lu, X. Ji, Q. Zhou, D. Zhu, Nature Medicine 16 (2010) 1439–1443.","ieee":"L. Zhou <i>et al.</i>, “Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95,” <i>Nature Medicine</i>, vol. 16, no. 12. Nature Publishing Group, pp. 1439–1443, 2010.","ama":"Zhou L, Li F, Xu H, et al. Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. <i>Nature Medicine</i>. 2010;16(12):1439-1443. doi:<a href=\"https://doi.org/10.1038/nm.2245\">10.1038/nm.2245</a>","mla":"Zhou, L., et al. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced Interaction of NNOS with PSD-95.” <i>Nature Medicine</i>, vol. 16, no. 12, Nature Publishing Group, 2010, pp. 1439–43, doi:<a href=\"https://doi.org/10.1038/nm.2245\">10.1038/nm.2245</a>.","apa":"Zhou, L., Li, F., Xu, H., Luo, C., Wu, H., Zhu, M., … Zhu, D. (2010). Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. <i>Nature Medicine</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nm.2245\">https://doi.org/10.1038/nm.2245</a>","ista":"Zhou L, Li F, Xu H, Luo C, Wu H, Zhu M, Lu W, Ji X, Zhou Q, Zhu D. 2010. Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nature Medicine. 16(12), 1439–1443.","chicago":"Zhou, L, F Li, Haibing Xu, CX Luo, HY Wu, MM Zhu, W Lu, X Ji, QG Zhou, and DY Zhu. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced Interaction of NNOS with PSD-95.” <i>Nature Medicine</i>. Nature Publishing Group, 2010. <a href=\"https://doi.org/10.1038/nm.2245\">https://doi.org/10.1038/nm.2245</a>."},"external_id":{"pmid":["21102461"]},"month":"11","year":"2010","abstract":[{"lang":"eng","text":"Stroke is a major public health problem leading to high rates of death and disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are crucial for neuronal injury after stroke insult. However, directly inhibiting NMDARs or nNOS can cause severe side effects because they have key physiological functions in the CNS. Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95 interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction, ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively, had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke, perhaps without major side effects. "}],"intvolume":"        16","page":"1439-1443","publication_identifier":{"issn":["1078-8956","1546-170x"]},"publication_status":"published","quality_controlled":"1","publisher":"Nature Publishing Group","oa_version":"None","title":"Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95","author":[{"first_name":"L","last_name":"Zhou","full_name":"Zhou, L"},{"first_name":"F","full_name":"Li, F","last_name":"Li"},{"full_name":"Xu, Haibing","id":"310349D0-F248-11E8-B48F-1D18A9856A87","last_name":"Xu","first_name":"Haibing"},{"last_name":"Luo","full_name":"Luo, CX","first_name":"CX"},{"last_name":"Wu","full_name":"Wu, HY","first_name":"HY"},{"full_name":"Zhu, MM","last_name":"Zhu","first_name":"MM"},{"full_name":"Lu, W","last_name":"Lu","first_name":"W"},{"last_name":"Ji","full_name":"Ji, X","first_name":"X"},{"first_name":"QG","full_name":"Zhou, QG","last_name":"Zhou"},{"last_name":"Zhu","full_name":"Zhu, DY","first_name":"DY"}],"doi":"10.1038/nm.2245","day":"21","type":"journal_article","date_created":"2019-04-04T14:55:32Z","date_updated":"2021-01-12T08:06:43Z","_id":"6198","volume":16}]