1. Neuroscience

Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells

  1. Andrew T Landau
  2. Pojeong Park
  3. J David Wong-Campos
  4. He Tian
  5. Adam E Cohen
  6. Bernardo L Sabatini  Is a corresponding author
  1. Howard Hughes Medical Institute, Harvard Medical School, United States
  2. Harvard University, United States
https://doi.org/10.7554/eLife.76993
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Cite this article
  1. Andrew T Landau
  2. Pojeong Park
  3. J David Wong-Campos
  4. He Tian
  5. Adam E Cohen
  6. Bernardo L Sabatini
(2022)
Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells
eLife 11:e76993.
https://doi.org/10.7554/eLife.76993
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Abstract

Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation. Here, we reveal that bAPs fail to evoke calcium influx through voltage-gated calcium channels (VGCCs) in a specific population of dendritic branches in mouse cortical layer 2/3 pyramidal cells, despite evoking substantial VGCC-mediated calcium influx in sister branches. These branches contain VGCCs and successfully propagate bAPs in the absence of synaptic input; nevertheless, they fail to exhibit bAP-evoked calcium influx due to a branch-specific reduction in bAP amplitude. We demonstrate that these branches have more elaborate branch structure compared to sister branches, which causes a local reduction in electrotonic impedance and bAP amplitude. Finally, we show that bAPs still amplify synaptically-mediated calcium influx in these branches because of differences in the voltage-dependence and kinetics of VGCCs and NMDA-type glutamate receptors. Branch-specific compartmentalization of bAP-dependent calcium signals may provide a mechanism for neurons to diversify synaptic tuning across the dendritic tree.

Data availability

All data and code is posted on the Harvard Dataverse (doi:10.7910/DVN/ZHNKGE).

The following data sets were generated

Article and author information

Author details

  1. Andrew T Landau

    Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9105-1636

  2. Pojeong Park

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.

  3. J David Wong-Campos

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.

  4. He Tian

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    He Tian, has filed a patent on QuasAr6a (Application #: 63247704)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3282-7275

  5. Adam E Cohen

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    Adam E Cohen, has filed a patent for QuasAr6a (Application #: 63247704)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8699-2404

  6. Bernardo L Sabatini

    Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
    For correspondence
    bsabatini@hms.harvard.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0095-9177

Funding

National Institute of Neurological Disorders and Stroke (F31NS113353)

  • Andrew T Landau

National Institute of Neurological Disorders and Stroke (R37NS046579)

  • Bernardo L Sabatini

National Institute of Mental Health (1RF1MH117042-01)

  • Adam E Cohen

Defense Advanced Research Projects Agency (Vannevar Bush Faculty Fellowship)

  • Adam E Cohen

Brain Research Foundation (Scientific Innovation)

  • Adam E Cohen

Harvard Medical School (Harvard Brain Initiative)

  • Adam E Cohen
  • Bernardo L Sabatini

Life Sciences Research Foundation (Merck Awardee)

  • J David Wong-Campos

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

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Ethics

Animal experimentation: All procedures involving animals were in accordance with the National Institutes of Health Guide for the care and use of laboratory animals and were approved by the Harvard University Institutional Animal Care and Use Committee (IACUC) (Protocol #: IS00000571-3).

Version history

  1. Received: January 11, 2022
  2. Preprint posted: January 12, 2022 (view preprint)
  3. Accepted: March 22, 2022
  4. Accepted Manuscript published: March 23, 2022 (version 1)
  5. Version of Record published: April 4, 2022 (version 2)

Copyright

© 2022, Landau 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. Andrew T Landau
  2. Pojeong Park
  3. J David Wong-Campos
  4. He Tian
  5. Adam E Cohen
  6. Bernardo L Sabatini
(2022)
Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells
eLife 11:e76993.
https://doi.org/10.7554/eLife.76993

Share this article

https://doi.org/10.7554/eLife.76993

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