Homeostatic regulation through strengthening of neuronal network-correlated synaptic inputs

  1. Samuel J Barnes
  2. Georg B Keller
  3. Tara Keck  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. Friedrich Miescher Institute, Switzerland
  3. University College London, United Kingdom

Abstract

Homeostatic regulation is essential for stable neuronal function. Several synaptic mechanisms of homeostatic plasticity have been described, but the functional properties of synapses involved in homeostasis are unknown. We used longitudinal two-photon functional imaging of dendritic spine calcium signals in visual and retrosplenial cortices of awake adult mice to quantify the sensory deprivation-induced changes in the responses of functionally identified spines. We found that spines whose activity selectively correlated with intrinsic network activity underwent TNF-α dependent homeostatic increases in their response amplitudes, but spines identified as responsive to sensory stimulation did not. We observed an increase in the global sensory-evoked responses following sensory deprivation, despite the fact that the identified sensory inputs did not strengthen. Instead, global sensory-evoked responses correlated with the strength of network-correlated inputs. Our results suggest that homeostatic regulation of global responses is mediated through changes to intrinsic network-correlated inputs rather than changes to identified sensory inputs thought to drive sensory processing.

Data availability

The pre-processed raw data can be accessed at https://doi.org/10.5281/zenodo.7399602. Data that has not been pre-processed is available upon request to any interested party, due to size constraints, by emailing georg.keller@fmi.ch, who will provide temporary transfer access for downloading the data. No proposal is required to access the data and there are not restrictions on who can access the data. Software for controlling the two-photon microscope and pre-processing of the calcium imaging data is available on https://sourceforge.net/projects/iris-scanning/.

The following data sets were generated

Article and author information

Author details

  1. Samuel J Barnes

    Department of Brain Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Georg B Keller

    Friedrich Miescher Institute, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1401-0117
  3. Tara Keck

    Department of Neuroscience, University College London, London, United Kingdom
    For correspondence
    t.keck@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6623-1037

Funding

Wellcome Trust (212264/Z/18/Z)

  • Tara Keck

European Research Council (homeostasis_in_vivo)

  • Tara Keck

Royal Society (Wolfson Research Award)

  • Tara Keck

Novartis Stiftung für Medizinisch-Biologische Forschung

  • Georg B Keller

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

Ethics

Animal experimentation: Experiments were conducted in strict accordance with the United Kingdom Animals (Scientific Procedures) Act 1986, and were approved by the UCL Animal Welfare and Ethical Review Body (AWERB) and by the Veterinary Department of the Canton of Basel-Stadt, Switzerland.

Copyright

© 2022, Barnes 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. Samuel J Barnes
  2. Georg B Keller
  3. Tara Keck
(2022)
Homeostatic regulation through strengthening of neuronal network-correlated synaptic inputs
eLife 11:e81958.
https://doi.org/10.7554/eLife.81958

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https://doi.org/10.7554/eLife.81958