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Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model

Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in...

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Autores principales: Deng, Manfei, Zhang, Qingping, Wu, Zhuoze, Ma, Tian, He, Aodi, Zhang, Tongmei, Ke, Xiao, Yu, Quntao, Han, Yunyun, Lu, Youming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253057/
https://www.ncbi.nlm.nih.gov/pubmed/32222058
http://dx.doi.org/10.1111/acel.13144
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author Deng, Manfei
Zhang, Qingping
Wu, Zhuoze
Ma, Tian
He, Aodi
Zhang, Tongmei
Ke, Xiao
Yu, Quntao
Han, Yunyun
Lu, Youming
author_facet Deng, Manfei
Zhang, Qingping
Wu, Zhuoze
Ma, Tian
He, Aodi
Zhang, Tongmei
Ke, Xiao
Yu, Quntao
Han, Yunyun
Lu, Youming
author_sort Deng, Manfei
collection PubMed
description Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single‐cell RNA sequencing reveals that miR‐128 that binds to a 3′UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Silencing miR‐128 or disrupting miR‐128 binding to STIM2 evokes STIM2 expression, restores synaptic function, and rescues memory imprecision in AD mice. Comparable findings are achieved by directly engineering MCs with the expression of STIM2. This study unveils a key synaptic and molecular mechanism that dictates how memory maintains or losses its details and warrants a promising target for therapeutic intervention of memory decays in the early stage of AD.
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spelling pubmed-72530572020-06-01 Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model Deng, Manfei Zhang, Qingping Wu, Zhuoze Ma, Tian He, Aodi Zhang, Tongmei Ke, Xiao Yu, Quntao Han, Yunyun Lu, Youming Aging Cell Original Articles Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single‐cell RNA sequencing reveals that miR‐128 that binds to a 3′UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Silencing miR‐128 or disrupting miR‐128 binding to STIM2 evokes STIM2 expression, restores synaptic function, and rescues memory imprecision in AD mice. Comparable findings are achieved by directly engineering MCs with the expression of STIM2. This study unveils a key synaptic and molecular mechanism that dictates how memory maintains or losses its details and warrants a promising target for therapeutic intervention of memory decays in the early stage of AD. John Wiley and Sons Inc. 2020-03-28 2020-05 /pmc/articles/PMC7253057/ /pubmed/32222058 http://dx.doi.org/10.1111/acel.13144 Text en © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Deng, Manfei
Zhang, Qingping
Wu, Zhuoze
Ma, Tian
He, Aodi
Zhang, Tongmei
Ke, Xiao
Yu, Quntao
Han, Yunyun
Lu, Youming
Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title_full Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title_fullStr Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title_full_unstemmed Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title_short Mossy cell synaptic dysfunction causes memory imprecision via miR‐128 inhibition of STIM2 in Alzheimer's disease mouse model
title_sort mossy cell synaptic dysfunction causes memory imprecision via mir‐128 inhibition of stim2 in alzheimer's disease mouse model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253057/
https://www.ncbi.nlm.nih.gov/pubmed/32222058
http://dx.doi.org/10.1111/acel.13144
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