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

Krishnan, Keerthi, Lau, Billy, Ewall, Gabrielle, Huang, Josh, Shea, Stephen David (February 2016) MECP2 regulates cortical plasticity underlying a learned behavior in adult female mice. BioRxiv. (Unpublished)

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Abstract

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 sensitivity to social sensory cues reveals a role of MeCP2 mutations in facilitating adult plasticity that is distinct from their effects on early development.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > auditory cortex organism description > animal behavior > learning organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity
CSHL Authors:	Krishnan, Keerthi Lau, Billy Shea, Stephen D. Huang, Z. Josh
Communities:	CSHL labs > Huang lab CSHL labs > Shea lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	28 February 2016
Date Deposited:	24 May 2021 17:15
Last Modified:	24 May 2021 17:15
URI:	https://repository.cshl.edu/id/eprint/40147

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