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Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo

View ORCID ProfileJürgen Graf, View ORCID ProfileVahid Rahmati, View ORCID ProfileMyrtill Majoros, View ORCID ProfileOtto W. Witte, View ORCID ProfileChristian Geis, View ORCID ProfileStefan J. Kiebel, View ORCID ProfileKnut Holthoff, View ORCID ProfileKnut Kirmse
doi: https://doi.org/10.1101/2021.05.28.446133
Jürgen Graf
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
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Vahid Rahmati
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
2Section Translational Neuroimmunology, Jena University Hospital, 07747 Jena, Germany
3Department of Psychology, Technical University Dresden, 01187 Dresden, Germany
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Myrtill Majoros
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
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Otto W. Witte
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
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Christian Geis
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
2Section Translational Neuroimmunology, Jena University Hospital, 07747 Jena, Germany
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Stefan J. Kiebel
3Department of Psychology, Technical University Dresden, 01187 Dresden, Germany
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Knut Holthoff
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
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Knut Kirmse
1Department of Neurology, Jena University Hospital, 07747 Jena, Germany
4Department of Neurophysiology, Institute of Physiology, University of Würzburg, 97070 Würzburg, Germany
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  • For correspondence: knut.kirmse@uni-wuerzburg.de
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Abstract

Spontaneous correlated activity is a universal hallmark of immature neural circuits. However, the cellular dynamics and intrinsic mechanisms underlying network burstiness in the intact developing brain are largely unknown. Here, we use two-photon Ca2+ imaging to comprehensively map the developmental trajectories of spontaneous network activity in hippocampal area CA1 in vivo. We unexpectedly find that network burstiness peaks after the developmental emergence of effective synaptic inhibition in the second postnatal week. We demonstrate that the enhanced network burstiness reflects an increased functional coupling of individual neurons to local population activity. However, pairwise neuronal correlations are low, and network bursts (NBs) recruit CA1 pyramidal cells in a virtually random manner. Using a dynamic systems modeling approach, we reconcile these experimental findings and identify network bi-stability as a potential regime underlying network burstiness at this age. Our analyses reveal an important role of synaptic input characteristics and network instability dynamics for NB generation. Collectively, our data suggest a mechanism, whereby developing CA1 performs extensive input-discrimination learning prior to the onset of environmental exploration.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵6 Senior authors

  • Figure 2 revised; Figure 3 revised; Figure 6 added; Figure 9 added; text revised; Supplementary Information revised.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 19, 2022.
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Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo
Jürgen Graf, Vahid Rahmati, Myrtill Majoros, Otto W. Witte, Christian Geis, Stefan J. Kiebel, Knut Holthoff, Knut Kirmse
bioRxiv 2021.05.28.446133; doi: https://doi.org/10.1101/2021.05.28.446133
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Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo
Jürgen Graf, Vahid Rahmati, Myrtill Majoros, Otto W. Witte, Christian Geis, Stefan J. Kiebel, Knut Holthoff, Knut Kirmse
bioRxiv 2021.05.28.446133; doi: https://doi.org/10.1101/2021.05.28.446133

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