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Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice

The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The lateral entorhinal cortex (LEC) is tightly interconnected with both prefrontal cortex (PFC) and hippocampus (HP), yet its contribution to the early dysfunction is fully...

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Autores principales: Xu, Xiaxia, Song, Lingzhen, Kringel, Rebecca, Hanganu-Opatz, Ileana L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611076/
https://www.ncbi.nlm.nih.gov/pubmed/34815409
http://dx.doi.org/10.1038/s41467-021-27114-w
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author Xu, Xiaxia
Song, Lingzhen
Kringel, Rebecca
Hanganu-Opatz, Ileana L.
author_facet Xu, Xiaxia
Song, Lingzhen
Kringel, Rebecca
Hanganu-Opatz, Ileana L.
author_sort Xu, Xiaxia
collection PubMed
description The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The lateral entorhinal cortex (LEC) is tightly interconnected with both prefrontal cortex (PFC) and hippocampus (HP), yet its contribution to the early dysfunction is fully unknown. Here we show that mice that mimic the dual genetic (G) -environmental (E) etiology (GE mice) of psychiatric risk have poor LEC-dependent recognition memory at pre-juvenile age and abnormal communication within LEC-HP-PFC networks throughout development. These functional and behavioral deficits relate to sparser projections from LEC to CA1 and decreased efficiency of axonal terminals to activate the hippocampal circuits in neonatal GE mice. In contrast, the direct entorhinal drive to PFC is not affected, yet the PFC is indirectly compromised, as target of the under-activated HP. Thus, the entorhinal-hippocampal circuit is already impaired from neonatal age on in GE mice.
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spelling pubmed-86110762021-12-01 Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice Xu, Xiaxia Song, Lingzhen Kringel, Rebecca Hanganu-Opatz, Ileana L. Nat Commun Article The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The lateral entorhinal cortex (LEC) is tightly interconnected with both prefrontal cortex (PFC) and hippocampus (HP), yet its contribution to the early dysfunction is fully unknown. Here we show that mice that mimic the dual genetic (G) -environmental (E) etiology (GE mice) of psychiatric risk have poor LEC-dependent recognition memory at pre-juvenile age and abnormal communication within LEC-HP-PFC networks throughout development. These functional and behavioral deficits relate to sparser projections from LEC to CA1 and decreased efficiency of axonal terminals to activate the hippocampal circuits in neonatal GE mice. In contrast, the direct entorhinal drive to PFC is not affected, yet the PFC is indirectly compromised, as target of the under-activated HP. Thus, the entorhinal-hippocampal circuit is already impaired from neonatal age on in GE mice. Nature Publishing Group UK 2021-11-23 /pmc/articles/PMC8611076/ /pubmed/34815409 http://dx.doi.org/10.1038/s41467-021-27114-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Xiaxia
Song, Lingzhen
Kringel, Rebecca
Hanganu-Opatz, Ileana L.
Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title_full Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title_fullStr Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title_full_unstemmed Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title_short Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
title_sort developmental decrease of entorhinal-hippocampal communication in immune-challenged disc1 knockdown mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611076/
https://www.ncbi.nlm.nih.gov/pubmed/34815409
http://dx.doi.org/10.1038/s41467-021-27114-w
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