Activity-dependent neuroplasticity induced by an enriched environment reverses cognitive deficits in scribble deficient mouse

Muna L. Hilal, Maité M. Moreau, Claudia Racca, Vera L. Pinheiro, Nicolas H. Piguel, Marie Josée Santoni, Steve Dos Santos Carvalho, Jean Michel Blanc, Yah Se K. Abada, Ronan Peyroutou, Chantal Medina, Hélène Doat, Thomas Papouin, Laurent Vuillard, Jean Paul Borg, Rivka Rachel, Aude Panatier, Mireille Montcouquiol, Stéphane H.R. Oliet, Nathalie Sans

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)5635-5651
Number of pages17
JournalCerebral Cortex
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2017

Keywords

  • Consolidation memory
  • LTD
  • Phosphatases
  • Planar cell polarity
  • Synapse

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