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

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.

In mice, reactivation of neurons that express cFos during fear conditioning induces a behavioural response. Here the authors show that cFos expression in mouse dentate gyrus shifts every day to different neurons, even during highly consistent spatial navigation, and suggest this clock-like selection mechanism may aid the encoding of episodic memories.