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Nat Neurosci. 2018 Jul;21(7):996-1003. doi: 10.1038/s41593-018-0163-8. Epub 2018 Jun 4.

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

Author information

1
Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wakoshi, Saitama, Japan. stevenmiddleton@brain.riken.jp.
2
RIKEN Center for Brain Science, Wakoshi, Saitama, Japan. stevenmiddleton@brain.riken.jp.
3
Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wakoshi, Saitama, Japan.
4
RIKEN Center for Brain Science, Wakoshi, Saitama, Japan.
5
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wakoshi, Saitama, Japan.
6
Department of Physiology, Nippon Medical School, Tokyo, Japan.
7
Section of Neurobiology, University of California San Diego, California, La Jolla, USA.
8
RIKEN Center for Brain Science, Wakoshi, Saitama, Japan. yamakawa@brain.riken.jp.
9
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wakoshi, Saitama, Japan. yamakawa@brain.riken.jp.
10
Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wakoshi, Saitama, Japan. thomas.mchugh@riken.jp.
11
RIKEN Center for Brain Science, Wakoshi, Saitama, Japan. thomas.mchugh@riken.jp.
12
Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan. thomas.mchugh@riken.jp.

Abstract

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

PMID:
29867081
DOI:
10.1038/s41593-018-0163-8
[Indexed for MEDLINE]

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