Abstract

It is widely assumed that our actions shape our brains and that the resulting connections determine who we are. To test this idea in a reductionist setting, in which genes and environment are controlled, we investigated differences in neuroanatomy and structural covariance by ex vivo structural magnetic resonance imaging (MRI) in mice whose behavioral activity was continuously tracked for 3 months in a large, enriched environment. We confirmed that environmental enrichment increases mouse hippocampal volumes. Stratifying the enriched group according to individual longitudinal behavioral trajectories, however, revealed striking differences in mouse brain structural covariance in continuously highly active mice compared to those whose trajectories showed signs of habituating activity. Network-based statistics identified distinct sub-networks of murine structural covariance underlying these differences in behavioral activity. Together, these results reveal that differentiated behavioral trajectories of mice in an enriched environment are associated with differences in brain connectivity.

Data availability

The structural MR images used in this manuscript are publicly available on the OSF platform (https://osf.io/m7gpd/). The volumetric MRI data are found in Supplementary Files 1 (absolute values) and 2 (relative values). The behavioral data from the cage (animal IDs with time-stamped raw antenna contacts) are assessible at Dryad: https://doi.org/10.5061/dryad.bzkh189ds

The following data sets were generated

Article and author information

Author details

  1. Jadna Bogado Lopes

    German Center for Neurodegenerative Diseases, TU Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Anna N Senko

    German Center for Neurodegenerative Diseases, TU Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0885-0440
  3. Klaas Bahnsen

    Faculty of Medicine, TU Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5413-0359
  4. Daniel Geisler

    Faculty of Medicine, TU Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Eugene Kim

    Department of Neuroimaging, King's 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:" 0000-0003-0066-7051
  6. Michel Bernanos

    Department of Neuroimaging, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Diana Cash

    Department of Neuroimaging, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Stefan Ehrlich

    Faculty of Medicine, TU Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Anthony C Vernon

    Department of Basic and Clinical Neuroscience, King's College London, London, United Kingdom
    For correspondence
    anthony.vernon@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7305-1069
  10. Gerd Kempermann

    German Center for Neurodegenerative Diseases, TU Dresden, Dresden, Germany
    For correspondence
    gerd.kempermann@dzne.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5304-4061

Funding

Helmholtz Association (Basic Funding)

  • Anna N Senko
  • Gerd Kempermann

Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden (Basic Funding)

  • Anna N Senko
  • Gerd Kempermann

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (88881.129646/2016-01)

  • Jadna Bogado Lopes

Joachim Herz Stiftung

  • Jadna Bogado Lopes

Medical Research Council (New Investigator Research Grant MR/N025377/1 (AV); Centre Grant MR/N026063/1)

  • Anthony C Vernon

TransCampus (TransCampus Research Award)

  • Anthony C Vernon
  • Gerd Kempermann

Deutsche Forschungsgemeinschaft (EH 367/7-1)

  • Stefan Ehrlich

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

Ethics

Animal experimentation: The experiment was conducted in accordance with the applicable European and national regulations and approved by the local authority (Landesdirektion Sachsen, file number 7/2016 TVT DD24 5131-365-8-SAC). All analyses were performed in a blinded manner.

Copyright

© 2023, Bogado Lopes 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

  • 1,868
    views
  • 317
    downloads
  • 7
    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. Jadna Bogado Lopes
  2. Anna N Senko
  3. Klaas Bahnsen
  4. Daniel Geisler
  5. Eugene Kim
  6. Michel Bernanos
  7. Diana Cash
  8. Stefan Ehrlich
  9. Anthony C Vernon
  10. Gerd Kempermann
(2023)
Individual behavioral trajectories shape whole-brain connectivity in mice
eLife 12:e80379.
https://doi.org/10.7554/eLife.80379

Share this article

https://doi.org/10.7554/eLife.80379

Further reading

    1. Neuroscience
    Steven S Hou, Yuya Ikegawa ... Masato Maesako
    Tools and Resources

    γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720–670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

    1. Neuroscience
    Francesco Longo
    Insight

    The neurotransmitter dopamine helps form long-term memories by increasing the production of proteins through a unique signaling pathway.