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

Cereb Cortex. 2017 Dec 1;27(12):5635-5651. doi: 10.1093/cercor/bhw333.

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.

Keywords: LTD; consolidation memory; phosphatases; planar cell polarity; synapse.

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / physiopathology*
  • Cognitive Dysfunction / therapy*
  • Environment*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Housing, Animal
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Learning Disabilities / pathology
  • Learning Disabilities / physiopathology
  • Learning Disabilities / therapy
  • Male
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Memory Disorders / therapy
  • Mice, Knockout
  • Models, Molecular
  • Neuronal Plasticity / physiology*
  • Post-Synaptic Density / metabolism
  • Post-Synaptic Density / ultrastructure
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / metabolism
  • Synapses / ultrastructure

Substances

  • Intracellular Signaling Peptides and Proteins
  • Receptors, N-Methyl-D-Aspartate
  • scribble protein, mouse