Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
- RIKEN Brain Science Institute, Japan
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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
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)).
Reviewing Editor
- Eunjoon Kim, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Korea (South), Republic of
Publication history
- Received: August 25, 2017
- Accepted: February 25, 2018
- Accepted Manuscript published: February 27, 2018 (version 1)
- Version of Record published: March 7, 2018 (version 2)
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.
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