Activity-Dependent Neuroplasticity Induced by an Enriched Environment Reverses Cognitive Deficits in Scribble Deficient Mouse.
Cerebral Cortex. 2016-11-22; 27(12): 5635-5651
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Hilal ML(1)(2), Moreau MM(1)(2), Racca C(3), Pinheiro VL(1)(2), Piguel NH(1)(2), Santoni MJ(4)(5)(6)(7), Dos Santos Carvalho S(1)(2), Blanc JM(1)(8)(9), Abada YK(1)(2), Peyroutou R(1)(2), Medina C(1)(2), Doat H(1)(2), Papouin T(1)(2), Vuillard L(8), Borg JP(4)(5)(6)(7), Rachel R(10), Panatier A(1)(2), Montcouquiol M(1)(2), Oliet SHR(1)(2), Sans N(1)(2).
(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.
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.