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.

Metrics

  • 1,702
    views
  • 232
    downloads
  • 6
    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. 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

Share this article

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

Further reading

    1. Ecology
    2. Neuroscience
    Kathleen T Quach, Gillian A Hughes, Sreekanth H Chalasani
    Research Article

    Prey must balance predator avoidance with feeding, a central dilemma in prey refuge theory. Additionally, prey must assess predatory imminence—how close threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes: pre-encounter, post-encounter, and circa-strike, corresponding to increasing levels of threat—–suspecting, detecting, and contacting a predator. Although predatory risk often varies in spatial distribution and imminence, how these factors intersect to influence defensive behaviors is poorly understood. Integrating these factors into a naturalistic environment enables comprehensive analysis of multiple defense modes in consistent conditions. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, with Caenorhabditis elegans as prey and Pristionchus pacificus as predator. In a foraging environment comprised of a food-rich, high-risk patch and a food-poor, low-risk refuge, C. elegans innately exhibits circa-strike behaviors. With experience, it learns post- and pre-encounter behaviors that proactively anticipate threats. These defense modes intensify with predator lethality, with only life-threatening predators capable of eliciting all three modes. SEB-3 receptors and NLP-49 peptides, key stress regulators, vary in their impact and interdependence across defense modes. Overall, our model system reveals fine-grained insights into how stress-related signaling regulates defensive behaviors.

    1. Neuroscience
    Markus R Tünte, Stefanie Hoehl ... Ezgi Kayhan
    Research Advance

    Several recent theoretical accounts have posited that interoception, the perception of internal bodily signals, plays a vital role in early human development. Yet, empirical evidence of cardiac interoceptive sensitivity in infants to date has been mixed. Furthermore, existing evidence does not go beyond the perception of cardiac signals and focuses only on the age of 5–7 mo, limiting the generalizability of the results. Here, we used a modified version of the cardiac interoceptive sensitivity paradigm introduced by Maister et al., 2017 in 3-, 9-, and 18-mo-old infants using cross-sectional and longitudinal approaches. Going beyond, we introduce a novel experimental paradigm, namely the iBREATH, to investigate respiratory interoceptive sensitivity in infants. Overall, for cardiac interoceptive sensitivity (total n=135) we find rather stable evidence across ages with infants on average preferring stimuli presented synchronously to their heartbeat. For respiratory interoceptive sensitivity (total n=120) our results show a similar pattern in the first year of life, but not at 18 mo. We did not observe a strong relationship between cardiac and respiratory interoceptive sensitivity at 3 and 9 mo but found some evidence for a relationship at 18 mo. We validated our results using specification curve- and mega-analytic approaches. By examining early cardiac and respiratory interoceptive processing, we provide evidence that infants are sensitive to their interoceptive signals.