Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2

Lau, Billy, Krishnan, Keerthi, Huang, Josh, Shea, Stephen (May 2019) Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2. BioRxiv. (Unpublished)

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DOI: 10.1101/655035

Abstract

<h4>ABSTRACT</h4> The neurodevelopmental disorder Rett syndrome is caused by mutations in the gene Mecp2 . Misexpression of the protein MECP2 is thought to contribute to neuropathology by causing dysregulation of plasticity. Female heterozygous Mecp2 mutants ( Mecp2 het ) failed to acquire a learned maternal retrieval behavior when exposed to pups, an effect linked to disruption of parvalbumin-expressing inhibitory interneurons (PV+) in the auditory cortex. However, the consequences of dysregulated PV+ networks during early maternal experience for auditory cortical sensory activity are unknown. Here we show that maternal experience in wild-type adult female mice ( Mecp2 wt ) triggers suppression of PV+ auditory responses. We also observe concomitant disinhibition of auditory responses in deep-layer pyramidal neurons that is selective for behaviorally-relevant pup vocalizations. These neurons also exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Mecp2 het , yet a genetic manipulation of GABAergic networks that restores accurate retrieval behavior in Mecp2 het also restores maternal experience-dependent plasticity of PV+. Our data are consistent with a growing body of evidence that cortical networks are particularly vulnerable to mutations of Mecp2 in PV+ neurons.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic plasticity
CSHL Authors:
Communities: CSHL labs > Huang lab
CSHL labs > Shea lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 30 May 2019
Date Deposited: 24 May 2021 17:00
Last Modified: 24 May 2021 17:00
URI: https://repository.cshl.edu/id/eprint/40146

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