Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2
Open accessAbstract
Methyl-CpG-binding protein 2 (MeCP2) mutations are the primary cause of Rett syndrome, a severe neurodevelopmental disorder. Cortical parvalbumin GABAergic interneurons (PV) make exuberant somatic connections onto pyramidal cells in the visual cortex of Mecp2-deficient mice, which contributes to silencing neuronal cortical circuits. This phenotype can be rescued independently of Mecp2 by environmental, pharmacological, and genetic manipulation. It remains unknown how Mecp2 mutation can result in abnormal inhibitory circuit refinement. In the present manuscript, we examined the development of GABAergic circuits in the primary visual cortex of Mecp2-deficient mice. We identified that PV circuits were the only GABAergic interneurons to be upregulated, while other interneurons were downregulated. Acceleration of PV cell maturation was accompanied by increased PV cells engulfment by perineuronal nets (PNNs) and by an increase of PV cellular and PNN structural complexity. Interestingly, selective deletion of Mecp2 from PV cells was sufficient to drive increased structure complexity of PNN. Moreover, the accelerated PV and PNN maturation was recapitulated in organotypic cultures. Our results identify a specific timeline of disruption of GABAergic circuits in the absence of Mecp2, indicating a possible cell-autonomous role of MeCP2 in the formation of PV cellular arbors and PNN structures in the visual cortex.
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Rett syndrome is associated with larger denser PNNs around PV interneurons in the cortex and many neurons in hippocampal CA2, possibly due to decreased secretion of MMP-9.
“The condition is associated with larger denser PNNs around PV interneurons in the cortex and many neurons in hippocampal CA2 (which mediates social behaviours), possibly due to decreased secretion of the metalloproteinase MMP-9.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [180]
In a Rett syndrome model, there is an increase in the number and complexity of PNNs around PV interneurons in the cortex, altering cortical excitability.
“In the cortex there is also an increase in the number and complexity of PNNs around PV interneurons in a Rett syndrome model, altering cortical excitability [102, 180].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [180]
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The extracellular matrix and perineuronal nets in memory
Fawcett, J. W., Fyhn, M., Jendelova, P., Kwok, J. C. F., Ruzicka, J., & Sorg, B. A. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01634-3 · Cited by 169 · see citing works
- Authors
- Patrizi, A., Awad, P. N., Chattopadhyaya, B., Li, C., Di Cristo, G., & Fagiolini, M.
- Affiliations
- Boston Children's Hospital (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Department of Neurosciences, Université de Montréal, Montreal, Canada
- Corresponding author
- Patrizi, Annarita
- Fagiolini, Michela
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-04-30
- Volume
- 30
- Issue
- 1
- Pages
- 256-268
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC7029683
- OpenAlex
- W2942781492
- Cited by
- 46
- References
- 12
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 3
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nancy Lurie Marks Family Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (ROS1NS095959)
- Rett Syndrome Research Trust
- Simon Foundation
- Ste. Justine Foundation
- Scottish Rite Charitable Foundation of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- MeCP2, Rett syndrome, parvalbumin interneurons, GABAergic circuits, perineuronal nets, primary visual cortex, interneuron development, organotypic culture
- MeSH terms
- Animals, Interneurons, Male, Mice, Inbred C57BL, Neural Pathways, Parvalbumins, Visual Cortex, Mice, Knockout, Methyl-CpG-Binding Protein 2, GABAergic Neurons
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