1. Neuroscience
Download icon

Localized hypoxia within the SGZ determines the early survival of newborn hippocampal granule cells

  1. C Chatzi
  2. E Schnell
  3. G L Westbrook  Is a corresponding author
  1. Vollum Institute, United States
  2. Oregon Health & Science University, United States
Research Article
  • Cited 10
  • Views 1,583
  • Annotations
Cite this article as: eLife 2015;4:e08722 doi: 10.7554/eLife.08722


The majority of adult hippocampal newborn cells die during early differentiation from intermediate progenitors (IPCs) to immature neurons. Neural stem cells in vivo are located in a relative hypoxic environment, and hypoxia enhances their survival, proliferation and stemness in vitro. Thus, we hypothesized that migration of IPCs away from hypoxic zones within the SGZ might result in oxidative damage, thus triggering cell death. Hypoxic niches were observed along the SGZ, composed of adult NSCs and early IPCs, and oxidative byproducts were present in adjacent late IPCs and neuroblasts. Stabilizing hypoxia inducible factor-1α with dimethyloxallyl glycine increased early survival, but not proliferation or differentiation, in neurospheres in vitro and in newly born SGZ cells in vivo. Rescue experiments in Baxfl/fl mutants supported these results. We propose that localized hypoxia within the SGZ contributes to the neurogenic microenvironment and determines the early, activity-independent survival of adult hippocampal newborn cells.

Article and author information

Author details

  1. C Chatzi

    Vollum Institute, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. E Schnell

    Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. G L Westbrook

    Vollum Institute, Portland, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.


Animal experimentation: All procedures were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and have been conducted with the approval of the Institutional Animal Care and Use Committee (#IP00000148) and the Insitutional Biosafety Committee (#04-06) at Oregon Health and Science University.

Reviewing Editor

  1. Lee L Rubin, Harvard Stem Cell Institute, Harvard University, United States

Publication history

  1. Received: May 14, 2015
  2. Accepted: October 16, 2015
  3. Accepted Manuscript published: October 17, 2015 (version 1)
  4. Version of Record published: December 9, 2015 (version 2)


This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.


  • 1,583
    Page views
  • 302
  • 10

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Caroline S Lee et al.
    Research Article

    Learning about temporal structure is adaptive because it enables the generation of expectations. We examined how the brain uses experience in structured environments to anticipate upcoming events. During fMRI, individuals watched a 90-second movie clip six times. Using a Hidden Markov Model applied to searchlights across the whole brain, we identified temporal shifts between activity patterns evoked by the first vs. repeated viewings of the movie clip. In many regions throughout the cortex, neural activity patterns for repeated viewings shifted to precede those of initial viewing by up to 15 seconds. This anticipation varied hierarchically in a posterior (less anticipation) to anterior (more anticipation) fashion. We also identified specific regions in which the timing of the brain's event boundaries were related to those of human-labeled event boundaries, with the timing of this relationship shifting on repeated viewings. With repeated viewing, the brain's event boundaries came to precede human-annotated boundaries by 1-4 seconds on average. Together, these results demonstrate a hierarchy of anticipatory signals in the human brain and link them to subjective experiences of events.

    1. Neuroscience
    Hamid Karimi-Rouzbahani et al.
    Research Article Updated

    There are many monitoring environments, such as railway control, in which lapses of attention can have tragic consequences. Problematically, sustained monitoring for rare targets is difficult, with more misses and longer reaction times over time. What changes in the brain underpin these ‘vigilance decrements’? We designed a multiple-object monitoring (MOM) paradigm to examine how the neural representation of information varied with target frequency and time performing the task. Behavioural performance decreased over time for the rare target (monitoring) condition, but not for a frequent target (active) condition. This was mirrored in neural decoding using magnetoencephalography: coding of critical information declined more during monitoring versus active conditions along the experiment. We developed new analyses that can predict behavioural errors from the neural data more than a second before they occurred. This facilitates pre-empting behavioural errors due to lapses in attention and provides new insight into the neural correlates of vigilance decrements.