RT Journal Article SR Electronic T1 Neuronal FOS reports synchronized activity of presynaptic neurons JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.09.04.556168 DO 10.1101/2023.09.04.556168 A1 Margarita Anisimova A1 Paul J. Lamothe-Molina A1 Andreas Franzelin A1 Aman S. Aberra A1 Michael B. Hoppa A1 Christine E. Gee A1 Thomas G. Oertner YR 2023 UL http://biorxiv.org/content/early/2023/09/05/2023.09.04.556168.abstract 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.