Feb 28, 2016

MECP2 regulates cortical plasticity underlying a learned behavior in adult female mice

BioRxiv : the Preprint Server for Biology
Keerthi KrishnanStephen D Shea


Neurodevelopmental disorders begin with the emergence of inappropriate synaptic connectivity early in life, yet how the sustained disruption of experience-dependent plasticity aggravates symptoms in adulthood is unclear. Here we used pup retrieval learning to assay adult cortical plasticity in a female mouse model of Rett syndrome (MeCP2het). We show that auditory cortical plasticity and retrieval learning are impaired in MeCP2het. Specifically, normal MECP2 expression in the adult auditory cortex is required for efficient retrieval learning. In wild-type mice, cohabitation with a mother and her pups triggered transient changes to auditory cortical inhibitory networks, including elevated levels of the GABA-synthesizing enzyme GAD67. However, MeCP2het further exhibited increased expression of parvalbumin (PV) and perineuronal nets (PNNs), events thought to suppress plasticity at the closure of critical periods and in adult learning. Averting these events with genetic and pharmacological manipulations of the GABAergic network restored retrieval behavior. We propose that adult retrieval learning triggers a transient episode of inhibitory plasticity in the auditory cortex that is dysregulated in MeCP2het. This window of heightened ...Continue Reading

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Mentioned in this Paper

MECP2 wt Allele
Reparative Closure
Methyl-CpG-Binding Protein 2
Glutamate decarboxylase 1
Neurodevelopmental Disorders
PVALB gene
MECP2 gene
Synaptic Connectivity

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