Zeynep , Okur and Schlauri, Nadia and Bitsikas, Vassilis and Panopoulou, Myrto and Karmakar, Kajari and Schreiner, Dietmar and Scheiffele, Peter. (2023) Control of neuronal excitation-inhibition balance by BMP-SMAD1 signaling.
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Official URL: https://edoc.unibas.ch/94130/
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Abstract
Throughout life, neuronal networks in the mammalian neocortex maintain a balance of excitation and inhibition which is essential for neuronal computation. Deviations from a balanced state have been linked to neurodevelopmental disorders and severe disruptions result in epilepsy. To maintain balance, neuronal microcircuits composed of excitatory and inhibitory neurons sense alterations in neural activity and adjust neuronal connectivity and function. Here, we identified a signaling pathway in the adult mouse neocortex that is activated in response to elevated neuronal network activity. Over-activation of excitatory neurons is signaled to the network through the elevation of BMP2, a growth factor well-known for its role as morphogen in embryonic development. BMP2 acts on parvalbumin-expressing (PV) interneurons through the transcription factor SMAD1, which controls an array of glutamatergic synapse proteins and components of peri-neuronal nets. PV interneuron-specific impairment of BMP2-SMAD1 signaling is accompanied by a loss of PV cell glutamatergic innervation, underdeveloped peri-neuronal nets, and decreased excitability. Ultimately, this impairment of PV interneuron functional recruitment disrupts cortical excitation - inhibition balance with mice exhibiting spontaneous epileptic seizures. Our findings suggest that developmental morphogen signaling is re-purposed to stabilize cortical networks in the adult mammalian brain.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum 05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele) |
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UniBasel Contributors: | Scheiffele, Peter and Zeynep, Okur and Schlauri, Nadia and Bitsikas, Vassilis and Panopoulou, Myrto and Karmakar, Kajari and Schreiner, Dietmar and , |
Item Type: | Preprint |
Publisher: | bioRxiv |
Note: | Publication type according to Uni Basel Research Database: Discussion paper / Internet publication |
Language: | English |
Related URLs: | |
Identification Number: | |
edoc DOI: | |
Last Modified: | 27 Mar 2023 11:25 |
Deposited On: | 27 Mar 2023 11:25 |
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