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      Activity-Dependent Neuroplasticity Induced by an Enriched Environment Reverses Cognitive Deficits in Scribble Deficient Mouse

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          Abstract

          Planar cell polarity (PCP) signaling is well known to play a critical role during prenatal brain development; whether it plays specific roles at postnatal stages remains rather unknown. Here, we investigated the role of a key PCP-associated gene scrib in CA1 hippocampal structure and function at postnatal stages. We found that Scrib is required for learning and memory consolidation in the Morris water maze as well as synaptic maturation and NMDAR-dependent bidirectional plasticity. Furthermore, we unveiled a direct molecular interaction between Scrib and PP1/PP2A phosphatases whose levels were decreased in postsynaptic density of conditional knock-out mice. Remarkably, exposure to enriched environment (EE) preserved memory formation in CaMK-Scrib −/− mice by recovering synaptic plasticity and maturation. Thus, Scrib is required for synaptic function involved in memory formation and EE has beneficiary therapeutic effects. Our results demonstrate a distinct new role for a PCP-associated protein, beyond embryonic development, in cognitive functions during adulthood.

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          Author and article information

          Journal
          Cereb Cortex
          Cereb. Cortex
          cercor
          Cerebral Cortex (New York, NY)
          Oxford University Press
          1047-3211
          1460-2199
          December 2017
          22 November 2016
          01 December 2018
          : 27
          : 12
          : 5635-5651
          Affiliations
          [1 ] INSERM, Neurocentre Magendie, Unité U1215, F-33000 Bordeaux, France
          [2 ] University of Bordeaux , Neurocentre Magendie, U1215, F-33000 Bordeaux, France
          [3 ] Institute of Neuroscience, Newcastle University , Newcastle upon Tyne NE2 4HH, UK
          [4 ] CRCM, INSERM U1068, F-13009 Marseille, France
          [5 ] CRCM, CNRS UMR7258, F-13009 Marseille, France
          [6 ] Institut Paoli-Calmettes, F-13009 Marseille, France
          [7 ] Aix-Marseille Université , F-13007 Marseille, France
          [8 ] BioXtal Structural Biology Unit, Campus de Luminy, F-13288 Marseille, France
          [9 ] University of Bordeaux , Plateforme de Biochimie et de Biophysique des protéines, FR Bordeaux Neurocampus, F-33000 Bordeaux, France
          [10 ] Mouse Cancer Genetics Program, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA
          Author notes
          [* ]Address correspondence to Dr Nathalie Sans or Dr Mireille Montcouquiol, Planar Polarity and Plasticity Group, Neurocentre Magendie, U862, F-33000 Bordeaux, France. Email: nathalie.sans@ 123456inserm.fr
          [†]

          Equal contribution.

          [‡]

          Equal senior authorship.

          Article
          PMC5939200 PMC5939200 5939200 bhw333
          10.1093/cercor/bhw333
          5939200
          28968740
          b0df07a1-d5f5-49f1-8cbc-e96f58ba147a
          © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
          History
          : 24 February 2016
          : 05 August 2016
          Page count
          Pages: 17
          Funding
          Funded by: National Institutes of Health 10.13039/100000002
          Funded by: National Research Agency 10.13039/501100001665
          Award ID: ANR-07-NEUR-031-01
          Award ID: ANR-12-BSV4-0016-01
          Funded by: National Institute of Health and Medical Research 10.13039/501100001677
          Funded by: Conseil Régional d'Aquitaine
          Funded by: La Fondation pour la Recherche Médicale
          Award ID: FDT20120925405
          Award ID: FDT20130928124
          Categories
          Original Articles

          planar cell polarity,phosphatases,consolidation memory,LTD,synapse

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