Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells
- Howard Hughes Medical Institute, Harvard Medical School, United States
- Harvard University, United States
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).
Article and author information
Author details
Bernardo L Sabatini
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.
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).
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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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
