| Autor: |
Nazim Kourdougli, Anand Suresh, Benjamin Liu, Pablo Juarez, Ashley Lin, David T. Chung, Anette Graven Sams, Michael Gandal, Verónica Martínez-Cerdeño, Dean V. Buonomano, Benjamin J. Hall, Cédric Mombereau, Carlos Portera-Cailliau |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.17.492368 |
| Popis: |
SUMMARYChanges in the function of inhibitory interneurons (INs) during cortical development could contribute to the pathophysiology of neurodevelopmental disorders. Using all-optical in vivo approaches in postnatal mouse somatosensory cortex (S1), we find that parvalbumin (PV) IN precursors are hypoactive and decoupled from excitatory neurons in Fmr1−/− mice, a model of Fragile X Syndrome (FXS). This leads to a loss of PV-INs in both mice and humans with FXS. Increasing the activity of future PV-INs in neonatal Fmr1−/− mice restores PV density and ameliorates transcriptional dysregulation in S1, but not circuit dysfunction. Critically, administering a novel allosteric modulator of Kv3.1 channels after the S1 critical period does rescue circuit dynamics and tactile defensiveness. Symptoms in FXS and related disorders could be mitigated by targeting PV-INs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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