CD40 is a major regulator of dendrite growth from developing excitatory and inhibitory neurons

  1. Paulina Carriba
  2. Alun M Davies  Is a corresponding author
  1. Cardiff University, United Kingdom

Abstract

Dendrite size and morphology are key determinants of the functional properties of neurons and neural circuits. Here we show that CD40, a member of the TNF receptor superfamily, is a major regulator of dendrite growth and elaboration in the developing brain. The dendrites of hippocampal excitatory neurons were markedly stunted in Cd40-/- mice, whereas those of striatal inhibitory neurons were much more exuberant. These striking and opposite phenotypic changes were also observed in excitatory and inhibitory neurons cultured from Cd40-/- mice and were rescued by soluble CD40. The changes in excitatory and inhibitory neurons cultured from Cd40-/- mice were mimicked in neurons of Cd40+/+ mice by treatment with soluble CD40L and were dependent on PKC-b and PKC-g, respectively. These results suggest that CD40-activated CD40L reverse signalling has striking and opposite effects on the growth and elaboration of dendrites among major classes of brain neurons by PKC-dependent mechanisms.

Article and author information

Author details

  1. Paulina Carriba

    School of Biosciences, Cardiff University, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Alun M Davies

    School of Biosciences, Cardiff University, Cardiff, United Kingdom
    For correspondence
    DaviesAlun@cardiff.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5841-8176

Funding

Wellcome Trust (103852)

  • Alun M Davies

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

Ethics

Animal experimentation: Mouse breeding and housing was approved by the Cardiff University Ethical Review Board and was performed within the remit of Home Office Licence PPL303081.

Copyright

© 2017, Carriba & Davies

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

  • 1,850
    views
  • 295
    downloads
  • 23
    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. Paulina Carriba
  2. Alun M Davies
(2017)
CD40 is a major regulator of dendrite growth from developing excitatory and inhibitory neurons
eLife 6:e30442.
https://doi.org/10.7554/eLife.30442

Share this article

https://doi.org/10.7554/eLife.30442

Further reading

    1. Neuroscience
    Olga Kepinska, Josue Dalboni da Rocha ... Narly Golestani
    Research Article

    This study examines whether auditory cortex anatomy reflects multilingual experience, specifically individuals’ phonological repertoire. Using data from over 200 participants exposed to 1–7 languages across 36 languages, we analyzed the role of language experience and typological distances between languages they spoke in shaping neural signatures of multilingualism. Our findings reveal a negative relationship between the thickness of the left and right second transverse temporal gyrus (TTG) and participants’ degree of multilingualism. Models incorporating phoneme-level information in the language experience index explained the most variance in TTG thickness, suggesting that a more extensive and more phonologically diverse language experience is associated with thinner cortices in the second TTG. This pattern, consistent across two datasets, supports the idea of experience-driven pruning and neural efficiency. Our findings indicate that experience with typologically distant languages appear to impact the brain differently than those with similar languages. Moreover, they suggest that early auditory regions seem to represent phoneme-level cross-linguistic information, contrary to the most established models of language processing in the brain, which suggest that phonological processing happens in more lateral posterior superior temporal gyrus (STG) and superior temporal sulcus (STS).

    1. Neuroscience
    Sara A Nolin, Mary E Faulkner ... Kristina Visscher
    Research Article

    The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain's organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry. We found that the segregation of the association system and the individual networks within the association system [the fronto-parietal network (FPN), cingulo-opercular network (CON) and default mode network (DMN)], has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.