1. Neuroscience

Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum

  1. Peter H Chipman
  2. Chi Chung Alan Fung
  3. Alejandra Pazo Fernandez
  4. Abhilash Sawant
  5. Angelo Tedoldi
  6. Atsushi Kawai
  7. Sunita Ghimire Gautam
  8. Mizuki Kurosawa
  9. Manabu Abe
  10. Kenji Sakimura
  11. Tomoki Fukai
  12. Yukiko Goda  Is a corresponding author
  1. RIKEN, Japan
  2. Okinawa Institute of Science and Technology Graduate University, Japan
  3. Brain Research Institute, Niigata University, Japan
  4. Niigata University, Japan
https://doi.org/10.7554/eLife.70818
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Cite this article
  1. Peter H Chipman
  2. Chi Chung Alan Fung
  3. Alejandra Pazo Fernandez
  4. Abhilash Sawant
  5. Angelo Tedoldi
  6. Atsushi Kawai
  7. Sunita Ghimire Gautam
  8. Mizuki Kurosawa
  9. Manabu Abe
  10. Kenji Sakimura
  11. Tomoki Fukai
  12. Yukiko Goda
(2021)
Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
eLife 10:e70818.
https://doi.org/10.7554/eLife.70818
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Abstract

Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs although their exact function has remained controversial. Here we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3 and 4.

Article and author information

Author details

  1. Peter H Chipman

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  2. Chi Chung Alan Fung

    Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Japan
    Competing interests
    No competing interests declared.

  3. Alejandra Pazo Fernandez

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  4. Abhilash Sawant

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  5. Angelo Tedoldi

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  6. Atsushi Kawai

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  7. Sunita Ghimire Gautam

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  8. Mizuki Kurosawa

    RIKEN, Wako-shi, Saitama, Japan
    Competing interests
    No competing interests declared.

  9. Manabu Abe

    Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan
    Competing interests
    No competing interests declared.

  10. Kenji Sakimura

    Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan
    Competing interests
    No competing interests declared.

  11. Tomoki Fukai

    Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Japan
    Competing interests
    No competing interests declared.

  12. Yukiko Goda

    RIKEN, Wako-shi, Saitama, Japan
    For correspondence
    yukiko.goda@riken.jp
    Competing interests
    Yukiko Goda, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0352-9498

Funding

Japan Society for the Promotion of Science (Overseas Research Fellow (P14760))

  • Peter H Chipman

Japan Society for the Promotion of Science (Core-to-Core Program (JPJSCCA20170008))

  • Yukiko Goda

MEXT Grants in Aid for Scientific Research (15H04280)

  • Yukiko Goda

MEXT Grants in Aid for Scientific Research (18H05213)

  • Tomoki Fukai

RIKEN Center for Brain Science

  • Yukiko Goda

Uehara Memorial Foundation

  • Yukiko Goda

Japan AMED Brain/MINDS

  • Yukiko Goda

MEXT Grants in Aid for Scientific Research (19K16885)

  • Chi Chung Alan Fung

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 experiments were approved by the RIKEN Animal Experiments Committee and performed in accordance with the RIKEN rules and guidelines. [Animal Experiment Plan Approval no. W2021-2-015(2)]

Copyright

© 2021, Chipman 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.

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  1. Peter H Chipman
  2. Chi Chung Alan Fung
  3. Alejandra Pazo Fernandez
  4. Abhilash Sawant
  5. Angelo Tedoldi
  6. Atsushi Kawai
  7. Sunita Ghimire Gautam
  8. Mizuki Kurosawa
  9. Manabu Abe
  10. Kenji Sakimura
  11. Tomoki Fukai
  12. Yukiko Goda
(2021)
Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
eLife 10:e70818.
https://doi.org/10.7554/eLife.70818

Share this article

https://doi.org/10.7554/eLife.70818

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