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

Lau, B. Y. B., Krishnan, K., Huang, Z. J., Shea, S. D. (January 2020) Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2. J Neurosci, 40 (7). pp. 1514-1526. ISSN 0270-6474

Abstract

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. Nevertheless, how dysregulated PV networks affect the neural activity dynamics that underlie auditory cortical plasticity during early maternal experience is unknown. Here we show that maternal experience in wild-type adult female mice (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 further exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Mecp2(het) , suggesting that they are an essential component of maternal learning. This is further supported by our finding that 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. Moreover, our work links, for the first time, impaired in vivo cortical plasticity in awake Mecp2 mutant animals to a natural, ethologically-relevant behavior.SIGNIFICANCE STATEMENTRett syndrome is a genetic disorder that includes language communication problems. Nearly all Rett syndrome is caused by mutations in the gene that produces the protein MECP2, which is important for changes in brain connectivity believed to underlie learning. We previously showed that female Mecp2 mutants fail to learn a simple maternal care behavior performed in response to their pups' distress cries. This impairment appeared to critically involve inhibitory neurons in the auditory cortex called parvalbumin neurons. Here we record from these neurons before and after maternal experience, and we show that they adapt their response to pup calls during maternal learning in non-mutants, but not in mutants. This adaptation is partially restored by a manipulation that improves learning.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > small molecules > GABA bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal organism description > animal behavior organs, tissues, organelles, cell types and functions > tissues types and functions > auditory cortex organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organism description > animal > mammal organism description > animal behavior > maternal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > MECP2 organism description > animal > mammal > rodent > mouse 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 types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Shea, Stephen D. Huang, Z. Josh Lau, Billy Krishnan, Keerthi
Communities:	CSHL labs > Huang lab CSHL labs > Shea lab
Depositing User:	Adrian Gomez
Date:	6 January 2020
Date Deposited:	09 Jan 2020 19:23
Last Modified:	30 Jan 2024 21:23
PMCID:	PMC7044728
Related URLs:	Publisher bioRxiv
URI:	https://repository.cshl.edu/id/eprint/38893

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