Population coupling predicts the plasticity of stimulus responses in cortical circuits

  1. Yann Sweeney
  2. Claudia Clopath  Is a corresponding author
  1. Imperial College London, United Kingdom

Abstract

Some neurons have stimulus responses that are stable over days, whereas other neurons have highly plastic stimulus responses. Using a recurrent network model, we explore whether this could be due to an underlying diversity in their synaptic plasticity. We find that, in a network with diverse learning rates, neurons with fast rates are more coupled to population activity than neurons with slow rates. This plasticity-coupling link predicts that neurons with high population coupling exhibit more long-term stimulus response variability than neurons with low population coupling. We substantiate this prediction using recordings from the Allen Brain Observatory, finding that a neuron's population coupling is correlated with the plasticity of its orientation preference. Simulations of a simple perceptual learning task suggest a particular functional architecture: a stable 'backbone' of stimulus representation formed by neurons with low population coupling, on top of which lies a flexible substrate of neurons with high population coupling.

Data availability

All calcium imaging data came from the Allen Institute for Brain Science, Allen Brain Observatory. Available from: http://observatory.brain-map.org/visualcoding/A list of experiment IDs can be found on FigShare, under the doi 10.6084/m9.figshare.11837406Code has been made available at https://github.com/yannaodh/sweeney_clopath_2020 and is under the doi:10.5281/zenodo.3757305.Previously Published Datasets: Allen Brain Observatory: Allen Institute, 2016, http://observatory.brain-map.org/visualcoding/, http://observatory.brain-map.org/visualcoding/

Article and author information

Author details

  1. Yann Sweeney

    Department of Bioengineering, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2164-2438
  2. Claudia Clopath

    Department of Bioengineering, Imperial College London, London, United Kingdom
    For correspondence
    c.clopath@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4507-8648

Funding

Biotechnology and Biological Sciences Research Council (BB/N013956/1,BB/N019008/1)

  • Claudia Clopath

Wellcome (200790/Z/16/Z)

  • Claudia Clopath

Engineering and Physical Sciences Research Council (EP/R035806/1)

  • Claudia Clopath

Simons Foundation (564408)

  • Claudia Clopath

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Version history

  1. Received: February 14, 2020
  2. Accepted: April 16, 2020
  3. Accepted Manuscript published: April 21, 2020 (version 1)
  4. Version of Record published: May 14, 2020 (version 2)

Copyright

© 2020, Sweeney & Clopath

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

  • 2,331
    Page views
  • 427
    Downloads
  • 16
    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. Yann Sweeney
  2. Claudia Clopath
(2020)
Population coupling predicts the plasticity of stimulus responses in cortical circuits
eLife 9:e56053.
https://doi.org/10.7554/eLife.56053

Share this article

https://doi.org/10.7554/eLife.56053

Further reading

    1. Developmental Biology
    2. Neuroscience
    Tariq Zaman, Daniel Vogt ... Michael R Williams
    Research Article

    The cell-type-specific expression of ligand/receptor and cell-adhesion molecules is a fundamental mechanism through which neurons regulate connectivity. Here, we determine a functional relevance of the long-established mutually exclusive expression of the receptor tyrosine kinase Kit and the trans-membrane protein Kit Ligand by discrete populations of neurons in the mammalian brain. Kit is enriched in molecular layer interneurons (MLIs) of the cerebellar cortex (i.e., stellate and basket cells), while cerebellar Kit Ligand is selectively expressed by a target of their inhibition, Purkinje cells (PCs). By in vivo genetic manipulation spanning embryonic development through adulthood, we demonstrate that PC Kit Ligand and MLI Kit are required for, and capable of driving changes in, the inhibition of PCs. Collectively, these works in mice demonstrate that the Kit Ligand/Kit receptor dyad sustains mammalian central synapse function and suggest a rationale for the affiliation of Kit mutation with neurodevelopmental disorders.

    1. Neuroscience
    Hideo Hagihara, Hirotaka Shoji ... Tsuyoshi Miyakawa
    Research Article

    Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.