PT  - JOURNAL ARTICLE
AU  - Margarita Anisimova
AU  - Paul J. Lamothe-Molina
AU  - Andreas Franzelin
AU  - Aman S. Aberra
AU  - Michael B. Hoppa
AU  - Christine E. Gee
AU  - Thomas G. Oertner
TI  - Neuronal FOS reports synchronized activity of presynaptic neurons
AID  - 10.1101/2023.09.04.556168
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.09.04.556168
4099  - http://biorxiv.org/content/early/2023/09/05/2023.09.04.556168.short
4100  - http://biorxiv.org/content/early/2023/09/05/2023.09.04.556168.full
AB  - 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 StatementThe authors have declared no competing interest.