ΔFosB accumulation in hippocampal granule cells drives cFos pattern separation during spatial learning

Paul J. Lamothe-Molina (), Andreas Franzelin, Lennart Beck, Dong Li, Lea Auksutat, Tim Fieblinger, Laura Laprell, Joachim Alhbeck, Christine E. Gee, Matthias Kneussel, Andreas K. Engel, Claus C. Hilgetag, Fabio Morellini and Thomas G. Oertner ()
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Paul J. Lamothe-Molina: University Medical Center Hamburg-Eppendorf
Andreas Franzelin: University Medical Center Hamburg-Eppendorf
Lennart Beck: University Medical Center Hamburg-Eppendorf
Dong Li: University Medical Center Hamburg-Eppendorf
Lea Auksutat: University Medical Center Hamburg-Eppendorf
Tim Fieblinger: University Medical Center Hamburg-Eppendorf
Laura Laprell: University Medical Center Hamburg-Eppendorf
Joachim Alhbeck: University Medical Center Hamburg-Eppendorf
Christine E. Gee: University Medical Center Hamburg-Eppendorf
Matthias Kneussel: University Medical Center Hamburg-Eppendorf
Andreas K. Engel: University Medical Center Hamburg-Eppendorf
Claus C. Hilgetag: University Medical Center Hamburg-Eppendorf
Fabio Morellini: University Medical Center Hamburg-Eppendorf
Thomas G. Oertner: University Medical Center Hamburg-Eppendorf

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Mice display signs of fear when neurons that express cFos during fear conditioning are artificially reactivated. This finding gave rise to the notion that cFos marks neurons that encode specific memories. Here we show that cFos expression patterns in the mouse dentate gyrus (DG) change dramatically from day to day in a water maze spatial learning paradigm, regardless of training level. Optogenetic inhibition of neurons that expressed cFos on the first training day affected performance days later, suggesting that these neurons continue to be important for spatial memory recall. The mechanism preventing repeated cFos expression in DG granule cells involves accumulation of ΔFosB, a long-lived splice variant of FosB. CA1 neurons, in contrast, repeatedly expressed cFos. Thus, cFos-expressing granule cells may encode new features being added to the internal representation during the last training session. This form of timestamping is thought to be required for the formation of episodic memories.

Date: 2022
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DOI: 10.1038/s41467-022-33947-w

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