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

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The immediate early gene cFos is often considered a marker for neurons involved in memory encoding.
• Artificial reactivation of cFos-expressing neurons can induce fear recall, supporting the idea that cFos marks specific memory engrams.

Purpose of the Study:

• To investigate the dynamic nature of cFos expression in the dentate gyrus during spatial learning.
• To determine the role of cFos-expressing neurons in spatial memory recall and formation.
• To elucidate the molecular mechanisms underlying differential cFos expression in hippocampal subregions.

Main Methods:

• Utilized a water maze spatial learning paradigm in mice.
• Employed optogenetics to inhibit specific neuronal populations identified by cFos expression.
• Analyzed cFos and FosB expression patterns in the dentate gyrus (DG) and CA1 regions.

Main Results:

• cFos expression patterns in the DG varied significantly from day to day, irrespective of training intensity.
• Inhibition of DG neurons expressing cFos on an initial training day impacted later spatial memory performance.
• DG granule cells showed limited re-expression of cFos, linked to accumulating ΔFosB, while CA1 neurons repeatedly expressed cFos.

Conclusions:

• cFos expression in the DG is dynamic and may serve to timestamp newly acquired information during spatial learning.
• These transiently labeled neurons are critical for the recall of spatial memories.
• Differential regulation of cFos expression, involving FosB, contributes to distinct roles of hippocampal subregions in memory formation and recall, potentially supporting episodic memory.