---
_id: '5828'
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.
article_processing_charge: No
article_type: original
author:
- first_name: Haibing
  full_name: Xu, Haibing
  id: 310349D0-F248-11E8-B48F-1D18A9856A87
  last_name: Xu
- first_name: Peter
  full_name: Baracskay, Peter
  id: 361CC00E-F248-11E8-B48F-1D18A9856A87
  last_name: Baracskay
- 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: 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>
  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>.
  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.
  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.
  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>.
  short: H. Xu, P. Baracskay, J. O’Neill, J.L. Csicsvari, Neuron 101 (2019) 119–132.e4.
date_created: 2019-01-13T22:59:10Z
date_published: 2019-01-02T00:00:00Z
date_updated: 2023-09-07T12:06:37Z
day: '02'
department:
- _id: JoCs
doi: 10.1016/j.neuron.2018.11.015
ec_funded: 1
external_id:
  isi:
  - '000454791500014'
intvolume: '       101'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.doi.org/10.1016/j.neuron.2018.11.015
month: '01'
oa: 1
oa_version: Published Version
page: 119-132.e4
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
publication: Neuron
publication_identifier:
  issn:
  - '10974199'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/reading-rats-minds/
  record:
  - id: '837'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Assembly responses of hippocampal CA1 place cells predict learned behavior
  in goal-directed spatial tasks on the radial eight-arm maze
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 101
year: '2019'
...
---
_id: '837'
abstract:
- lang: eng
  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. '
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. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Haibing
  full_name: Xu, Haibing
  id: 310349D0-F248-11E8-B48F-1D18A9856A87
  last_name: Xu
citation:
  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>
  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>
  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>.
  ieee: H. Xu, “Reactivation of the hippocampal cognitive map in goal-directed spatial
    tasks,” Institute of Science and Technology Austria, 2017.
  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>.
  short: H. Xu, Reactivation of the Hippocampal Cognitive Map in Goal-Directed Spatial
    Tasks, Institute of Science and Technology Austria, 2017.
date_created: 2018-12-11T11:48:46Z
date_published: 2017-08-23T00:00:00Z
date_updated: 2023-09-07T12:06:38Z
day: '23'
ddc:
- '571'
degree_awarded: PhD
department:
- _id: JoCs
doi: 10.15479/AT:ISTA:th_858
file:
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  checksum: f11925fbbce31e495124b6bc4f10573c
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dernst
  date_created: 2019-04-05T08:59:51Z
  date_updated: 2020-07-14T12:48:12Z
  file_id: '6213'
  file_name: 2017_Xu_Haibing_Thesis_Source.docx
  file_size: 3589490
  relation: source_file
- access_level: open_access
  checksum: ffb10749a537d615fab1ef0937ccb157
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  creator: dernst
  date_created: 2019-04-05T08:59:51Z
  date_updated: 2020-07-14T12:48:12Z
  file_id: '6214'
  file_name: 2017_Xu_Thesis_IST.pdf
  file_size: 11668613
  relation: main_file
file_date_updated: 2020-07-14T12:48:12Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '93'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6811'
pubrep_id: '858'
related_material:
  record:
  - id: '5828'
    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: Reactivation of the hippocampal cognitive map in goal-directed spatial tasks
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2017'
...
---
_id: '6198'
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. '
author:
- first_name: L
  full_name: Zhou, L
  last_name: Zhou
- first_name: F
  full_name: Li, F
  last_name: Li
- first_name: Haibing
  full_name: Xu, Haibing
  id: 310349D0-F248-11E8-B48F-1D18A9856A87
  last_name: Xu
- first_name: CX
  full_name: Luo, CX
  last_name: Luo
- first_name: HY
  full_name: Wu, HY
  last_name: Wu
- first_name: MM
  full_name: Zhu, MM
  last_name: Zhu
- first_name: W
  full_name: Lu, W
  last_name: Lu
- first_name: X
  full_name: Ji, X
  last_name: Ji
- first_name: QG
  full_name: Zhou, QG
  last_name: Zhou
- first_name: DY
  full_name: Zhu, DY
  last_name: Zhu
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2019-04-04T14:55:32Z
date_published: 2010-11-21T00:00:00Z
date_updated: 2021-01-12T08:06:43Z
day: '21'
doi: 10.1038/nm.2245
extern: '1'
external_id:
  pmid:
  - '21102461'
intvolume: '        16'
issue: '12'
language:
- iso: eng
month: '11'
oa_version: None
page: 1439-1443
pmid: 1
publication: Nature Medicine
publication_identifier:
  issn:
  - 1078-8956
  - 1546-170x
publication_status: published
publisher: Nature Publishing Group
quality_controlled: '1'
status: public
title: Treatment of cerebral ischemia by disrupting ischemia-induced interaction of
  nNOS with PSD-95
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2010'
...