Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice

Abstract

Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the 'over-suppression' theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice.

Article and author information

Author details

  1. Matthieu Raveau

    Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Denis Polygalov

    Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wako-shi, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8165-5257
  3. Roman Boehringer

    Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wako-shi, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2856-3262
  4. Kenji Amano

    Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Kazuhiro Yamakawa

    Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Japan
    For correspondence
    yamakawa@brain.riken.jp
    Competing interests
    The authors declare that no competing interests exist.
  6. Thomas J McHugh

    Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wako-shi, Japan
    For correspondence
    tjmchugh@brain.riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1243-5189

Funding

RIKEN Brain Science Institute

  • Kazuhiro Yamakawa
  • Thomas J McHugh

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

Ethics

Animal experimentation: All handling and experiments were conducted in accordance with the protocols approved by the RIKEN Animal Care and Use Committee (#H29-2-218(2) , # H29-2-224(3)).

Copyright

© 2018, Raveau 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

  • 1,979
    views
  • 277
    downloads
  • 22
    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. Matthieu Raveau
  2. Denis Polygalov
  3. Roman Boehringer
  4. Kenji Amano
  5. Kazuhiro Yamakawa
  6. Thomas J McHugh
(2018)
Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
eLife 7:e31543.
https://doi.org/10.7554/eLife.31543

Share this article

https://doi.org/10.7554/eLife.31543

Further reading

    1. Neuroscience
    Mi-Seon Kong, Ethan Ancell ... Larry S Zweifel
    Research Article

    The central amygdala (CeA) has emerged as an important brain region for regulating both negative (fear and anxiety) and positive (reward) affective behaviors. The CeA has been proposed to encode affective information in the form of valence (whether the stimulus is good or bad) or salience (how significant is the stimulus), but the extent to which these two types of stimulus representation occur in the CeA is not known. Here, we used single cell calcium imaging in mice during appetitive and aversive conditioning and found that majority of CeA neurons (~65%) encode the valence of the unconditioned stimulus (US) with a smaller subset of cells (~15%) encoding the salience of the US. Valence and salience encoding of the conditioned stimulus (CS) was also observed, albeit to a lesser extent. These findings show that the CeA is a site of convergence for encoding oppositely valenced US information.

    1. Neuroscience
    Raven Star Wallace, Bronte Mckeown ... Jonathan Smallwood
    Research Article

    Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.