Abstract

Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG) have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.

Data availability

All data generated or analysed during this study are included in the manuscript.

Article and author information

Author details

  1. Tamar Licht

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    For correspondence
    tamarli@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2333-1665
  2. Esther Sasson

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Batia Bell

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Myriam Grunewald

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Saran Kumar

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Tirzah Kreisel

    Edmond and Lily Safra Center for Brain Sciences (ELSC), Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Ayal Ben-Zvi

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Eli Keshet

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    For correspondence
    elik@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.

Funding

H2020 European Research Council (322692)

  • Tamar Licht
  • Myriam Grunewald
  • Saran Kumar
  • Eli Keshet

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the animal care and use committee of the Hebrew University (Protocol MD-14-13900-3). Every effort was made to minimize the numbers of animals and suffering.

Copyright

© 2020, Licht et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,277
    views
  • 376
    downloads
  • 36
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Tamar Licht
  2. Esther Sasson
  3. Batia Bell
  4. Myriam Grunewald
  5. Saran Kumar
  6. Tirzah Kreisel
  7. Ayal Ben-Zvi
  8. Eli Keshet
(2020)
Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes
eLife 9:e52134.
https://doi.org/10.7554/eLife.52134

Share this article

https://doi.org/10.7554/eLife.52134

Further reading

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.