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Neuronal FOS reports synchronized activity of presynaptic neurons

View ORCID ProfileMargarita Anisimova, View ORCID ProfilePaul J. Lamothe-Molina, View ORCID ProfileAndreas Franzelin, View ORCID ProfileAman S. Aberra, View ORCID ProfileMichael B. Hoppa, View ORCID ProfileChristine E. Gee, View ORCID ProfileThomas G. Oertner
doi: https://doi.org/10.1101/2023.09.04.556168
Margarita Anisimova
1Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, 20251 Germany
3Center for Neuroscience, 1544 Newton Court, Davis, CA 95618
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  • ORCID record for Margarita Anisimova
Paul J. Lamothe-Molina
1Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, 20251 Germany
4Institute of Pharmacology and Toxicology, University of Zürich, Zürich Switzerland
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Andreas Franzelin
1Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, 20251 Germany
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Aman S. Aberra
2Department of Biological Sciences, Dartmouth College, Hanover, NH, 03755 USA
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Michael B. Hoppa
2Department of Biological Sciences, Dartmouth College, Hanover, NH, 03755 USA
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Christine E. Gee
1Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, 20251 Germany
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Thomas G. Oertner
1Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, 20251 Germany
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  • For correspondence: thomas.oertner@zmnh.uni-hamburg.de
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Abstract

The immediate early gene FOS is frequently used as a marker for highly active neurons. Implicit in this use is the assumption that there is a correlation between neuronal spiking and FOS expression. Here we use optogenetic stimulation of hippocampal neurons to investigate the relation between spike frequency and FOS expression, and report several surprising observations. First, FOS expression is cell-type specific, spiking CA2 pyramidal neurons rarely express FOS. Second, FOS has a U-shaped dependence on frequency: Spiking at 0.1 Hz is more effective than high frequency spiking (50 Hz) while intermediate frequencies do not induce FOS. Third, the pathway from spiking to FOS is not cell-autonomous. Instead, transmitter release and metabotropic glutamate receptor (mGluR) activation are required and, at 0.1 Hz, FOS is induced independently of CREB/calcineurin/MEK pathways. We propose that FOS does not primarily encode a neuron’s own spike frequency but indicates repeated participation in highly synchronized activity, e.g. sharp wave ripples.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 05, 2023.
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Neuronal FOS reports synchronized activity of presynaptic neurons
Margarita Anisimova, Paul J. Lamothe-Molina, Andreas Franzelin, Aman S. Aberra, Michael B. Hoppa, Christine E. Gee, Thomas G. Oertner
bioRxiv 2023.09.04.556168; doi: https://doi.org/10.1101/2023.09.04.556168
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Neuronal FOS reports synchronized activity of presynaptic neurons
Margarita Anisimova, Paul J. Lamothe-Molina, Andreas Franzelin, Aman S. Aberra, Michael B. Hoppa, Christine E. Gee, Thomas G. Oertner
bioRxiv 2023.09.04.556168; doi: https://doi.org/10.1101/2023.09.04.556168

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