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Foxg1 Upregulation Enhances Neocortical Activity.

Authors :
Tigani W
Rossi MP
Artimagnella O
Santo M
Rauti R
Sorbo T
Ulloa Severino FP
Provenzano G
Allegra M
Caleo M
Ballerini L
Bozzi Y
Mallamaci A
Source :
Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2020 Jul 30; Vol. 30 (9), pp. 5147-5165.
Publication Year :
2020

Abstract

Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity. We found that mice overexpressing Foxg1 in neocortical pyramidal cells displayed an electroencephalography (EEG) with increased spike frequency and were more prone to kainic acid (KA)-induced seizures. Consistently, primary cultures of neocortical neurons gain-of-function for Foxg1 were hyperactive and hypersynchronized. That reflected an unbalanced expression of key genes encoding for ion channels, gamma aminobutyric acid and glutamate receptors, and was likely exacerbated by a pronounced interneuron depletion. We also detected a transient Foxg1 upregulation ignited in turn by neuronal activity and mediated by immediate early genes. Based on this, we propose that even small changes of Foxg1 levels may result in a profound impact on pyramidal cell activity, an issue relevant to neuronal physiology and neurological aberrancies associated to FOXG1 copy number variations.<br /> (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Details

Language :
English
ISSN :
1460-2199
Volume :
30
Issue :
9
Database :
MEDLINE
Journal :
Cerebral cortex (New York, N.Y. : 1991)
Publication Type :
Academic Journal
Accession number :
32383447
Full Text :
https://doi.org/10.1093/cercor/bhaa107