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Article

Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons

Institute of Physiology, University Medical Center Mainz, Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany
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Academic Editor: Thomas Knöpfel
Int. J. Mol. Sci. 2021, 22(12), 6575; https://doi.org/10.3390/ijms22126575
Received: 2 June 2021 / Revised: 16 June 2021 / Accepted: 16 June 2021 / Published: 19 June 2021
(This article belongs to the Collection Feature Papers in Molecular Neurobiology)
A substantial proportion of neurons undergoes programmed cell death (apoptosis) during early development. This process is attenuated by increased levels of neuronal activity and enhanced by suppression of activity. To uncover whether the mere level of activity or also the temporal structure of electrical activity affects neuronal death rates, we optogenetically controlled spontaneous activity of synaptically-isolated neurons in developing cortical cultures. Our results demonstrate that action potential firing of primary cortical neurons promotes neuronal survival throughout development. Chronic patterned optogenetic stimulation allowed to effectively modulate the firing pattern of single neurons in the absence of synaptic inputs while maintaining stable overall activity levels. Replacing the burst firing pattern with a non-physiological, single pulse pattern significantly increased cell death rates as compared to physiological burst stimulation. Furthermore, physiological burst stimulation led to an elevated peak in intracellular calcium and an increase in the expression level of classical activity-dependent targets but also decreased Bax/BCL-2 expression ratio and reduced caspase 3/7 activity. In summary, these results demonstrate at the single-cell level that the temporal pattern of action potentials is critical for neuronal survival versus cell death fate during cortical development, besides the pro-survival effect of action potential firing per se. View Full-Text
Keywords: cortex; development; apoptosis; optogenetics; activity pattern; burst; Bax; mouse cortex; development; apoptosis; optogenetics; activity pattern; burst; Bax; mouse
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MDPI and ACS Style

Wong Fong Sang, I.E.; Schroer, J.; Halbhuber, L.; Warm, D.; Yang, J.-W.; Luhmann, H.J.; Kilb, W.; Sinning, A. Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons. Int. J. Mol. Sci. 2021, 22, 6575. https://doi.org/10.3390/ijms22126575

AMA Style

Wong Fong Sang IE, Schroer J, Halbhuber L, Warm D, Yang J-W, Luhmann HJ, Kilb W, Sinning A. Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons. International Journal of Molecular Sciences. 2021; 22(12):6575. https://doi.org/10.3390/ijms22126575

Chicago/Turabian Style

Wong Fong Sang, I. E., Jonas Schroer, Lisa Halbhuber, Davide Warm, Jenq-Wei Yang, Heiko J. Luhmann, Werner Kilb, and Anne Sinning. 2021. "Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons" International Journal of Molecular Sciences 22, no. 12: 6575. https://doi.org/10.3390/ijms22126575

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