Cargando…
Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome
Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679137/ https://www.ncbi.nlm.nih.gov/pubmed/33215988 http://dx.doi.org/10.7554/eLife.61882 |
_version_ | 1783612286225612800 |
---|---|
author | Li, Jie Jiang, Rena Y Arendt, Kristin L Hsu, Yu-Tien Zhai, Sophia R Chen, Lu |
author_facet | Li, Jie Jiang, Rena Y Arendt, Kristin L Hsu, Yu-Tien Zhai, Sophia R Chen, Lu |
author_sort | Li, Jie |
collection | PubMed |
description | Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in Fmr1 KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the Fmr1 KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy. |
format | Online Article Text |
id | pubmed-7679137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-76791372020-11-23 Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome Li, Jie Jiang, Rena Y Arendt, Kristin L Hsu, Yu-Tien Zhai, Sophia R Chen, Lu eLife Neuroscience Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in Fmr1 KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the Fmr1 KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy. eLife Sciences Publications, Ltd 2020-11-20 /pmc/articles/PMC7679137/ /pubmed/33215988 http://dx.doi.org/10.7554/eLife.61882 Text en © 2020, Li et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Li, Jie Jiang, Rena Y Arendt, Kristin L Hsu, Yu-Tien Zhai, Sophia R Chen, Lu Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title | Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title_full | Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title_fullStr | Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title_full_unstemmed | Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title_short | Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome |
title_sort | defective memory engram reactivation underlies impaired fear memory recall in fragile x syndrome |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679137/ https://www.ncbi.nlm.nih.gov/pubmed/33215988 http://dx.doi.org/10.7554/eLife.61882 |
work_keys_str_mv | AT lijie defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome AT jiangrenay defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome AT arendtkristinl defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome AT hsuyutien defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome AT zhaisophiar defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome AT chenlu defectivememoryengramreactivationunderliesimpairedfearmemoryrecallinfragilexsyndrome |