Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human

  1. Petra Wahle  Is a corresponding author
  2. Eric Sobierajski
  3. Ina Gasterstädt
  4. Nadja Lehmann
  5. Susanna Weber
  6. Joachim HR Lübke
  7. Maren Engelhardt
  8. Claudia Distler
  9. Gundela Meyer
  1. Ruhr University Bochum, Germany
  2. Heidelberg University, Germany
  3. Research Centre Jülich GmbH, Germany
  4. Johannes Kepler University, Austria
  5. University of La Laguna, Spain

Abstract

The canonical view of neuronal function is that inputs are received by dendrites and somata, become integrated in the somatodendritic compartment and upon reaching a sufficient threshold, generate axonal output with axons emerging from the cell body. The latter is not necessarily the case. Instead, axons may originate from dendrites. The terms 'axon carrying dendrite' (AcD) and 'AcD neurons' have been coined to describe this feature. In rodent hippocampus, AcD cells are shown to be functionally 'privileged', since inputs here can circumvent somatic integration and lead to immediate action potential initiation in the axon. Here, we report on the diversity of axon origins in neocortical pyramidal cells of rodent, ungulate, carnivore, and primate. Detection methods were Thy-1-EGFP labeling in mouse, retrograde biocytin tracing in rat, cat, ferret, and macaque, SMI-32/βIV-spectrin immunofluorescence in pig, cat, and macaque, and Golgi staining in macaque and human. We found that in non-primate mammals, 10-21% of pyramidal cells of layers II-VI had an AcD. In marked contrast, in macaque and human, this proportion was lower, and was particularly low for supragranular neurons. A comparison of six cortical areas (sensory, association, limbic) in three macaques yielded percentages of AcD cells which varied by a factor of 2 between the areas and between the individuals. Unexpectedly, pyramidal cells in the white matter of postnatal cat and aged human cortex exhibit AcDs to much higher percentages. In addition, interneurons assessed in developing cat and adult human cortex had AcDs at type-specific proportions and for some types at much higher percentages than pyramidal cells. Our findings expand the current knowledge regarding the distribution and proportion of AcD cells in neocortex of non-primate taxa, which strikingly differ from primates where these cells are mainly found in deeper layers and white matter.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 3 , 4, 5, 6, 7

Article and author information

Author details

  1. Petra Wahle

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    For correspondence
    petra.wahle@rub.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8710-0375
  2. Eric Sobierajski

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ina Gasterstädt

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Nadja Lehmann

    Mannheim Center for Translational Neuroscience, Heidelberg University, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4801-3057
  5. Susanna Weber

    Mannheim Center for Translational Neuroscience, Heidelberg University, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Joachim HR Lübke

    Research Centre Jülich GmbH, Jülich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4086-3199
  7. Maren Engelhardt

    Faculty of Medicine, Johannes Kepler University, Linz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Claudia Distler

    Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Gundela Meyer

    Department of Basic Medical Science, University of La Laguna, Santa Cruz de Tenerife, Spain
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (WA 541/13-1)

  • Petra Wahle

Deutsche Forschungsgemeinschaft (WA 541/15-1)

  • Petra Wahle

Deutsche Forschungsgemeinschaft (EN 1240/2-1)

  • Maren Engelhardt

Deutsche Forschungsgemeinschaft (Ho-450/25-1)

  • Claudia Distler

Deutsche Forschungsgemeinschaft (SFB 509/A11)

  • Claudia Distler

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

Ethics

Human subjects: The data presented in this paper were collected via tissue sharing and from material that had originally been processed for projects not related to the present topic, i.e. no animals were sacrificed specifically for the present study. Human material was provided by Prof. Meyer and Prof. Lübke from previously published studies.

Reviewing Editor

  1. Kristine Krug, Otto-von-Guericke University Magdeburg, Germany

Publication history

  1. Received: December 3, 2021
  2. Preprint posted: December 27, 2021 (view preprint)
  3. Accepted: April 19, 2022
  4. Accepted Manuscript published: April 20, 2022 (version 1)

Copyright

© 2022, Wahle 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

  • 492
    Page views
  • 99
    Downloads
  • 0
    Citations

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)

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. Petra Wahle
  2. Eric Sobierajski
  3. Ina Gasterstädt
  4. Nadja Lehmann
  5. Susanna Weber
  6. Joachim HR Lübke
  7. Maren Engelhardt
  8. Claudia Distler
  9. Gundela Meyer
(2022)
Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human
eLife 11:e76101.
https://doi.org/10.7554/eLife.76101

Further reading

    1. Evolutionary Biology
    Jia Jia et al.
    Research Article

    Ecological preferences and life history strategies have enormous impacts on the evolution and phenotypic diversity of salamanders, but the yet established reliable ecological indicators from bony skeletons hinder investigations into the paleobiology of early salamanders. Here we statistically demonstrate, by using time-calibrated cladograms and geometric morphometric analysis on 71 specimens in 36 species, that both the shape of the palate and many non-shape covariates particularly associated with vomerine teeth are ecologically informative in early stem- and basal crown-group salamanders. Disparity patterns within the morphospace of the palate in ecological preferences, life history strategies and taxonomic affiliations were analyzed in detail, and evolutionary rates and ancestral states of the palate were reconstructed. Our results show that the palate is heavily impacted by convergence constrained by feeding mechanisms and also exhibits clear stepwise evolutionary patterns with alternative phenotypic configurations to cope with similar functional demand. Salamanders are diversified ecologically before the Middle Jurassic and achieved all their present ecological preferences in the Early Cretaceous. Our results reveal that the last common ancestor of all salamanders shares with other modern amphibians a unified biphasic ecological preference, and metamorphosis is significant in the expansion of ecomorphospace of the palate in early salamanders.

    1. Evolutionary Biology
    2. Genetics and Genomics
    Osvaldo Villa et al.
    Short Report Updated

    The influence of genetic variation on the aging process, including the incidence and severity of age-related diseases, is complex. Here, we define the evolutionarily conserved mitochondrial enzyme ALH-6/ALDH4A1 as a predictive biomarker for age-related changes in muscle health by combining Caenorhabditis elegans genetics and a gene-wide association scanning (GeneWAS) from older human participants of the US Health and Retirement Study (HRS). In a screen for mutations that activate oxidative stress responses, specifically in the muscle of C. elegans, we identified 96 independent genetic mutants harboring loss-of-function alleles of alh-6, exclusively. Each of these genetic mutations mapped to the ALH-6 polypeptide and led to the age-dependent loss of muscle health. Intriguingly, genetic variants in ALDH4A1 show associations with age-related muscle-related function in humans. Taken together, our work uncovers mitochondrial alh-6/ALDH4A1 as a critical component to impact normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.