Lysine crotonylation acts as an epigenetic switch for glutamate neurotransmission and spatial memory.

Spatial learning induces distinct spatiotemporal patterns of histone lysine crotonylation (Kcr) across hippocampal subregions, and crotonate-driven Kcr elevation enhances long-term memory.

• Why it matters: Histone lysine acetylation is known to regulate transcription for long-term memory, but whether non-acetyl acylations like Kcr control memory consolidation is unknown.
• What they did: The study mapped Kcr after spatial learning, then used genetic manipulations and crotonate administration to alter hippocampal Kcr; it combined single-nuclei transcriptome, chromatin accessibility, cell-cell communication, and real-time fluorescence imaging with genetically encoded sensors.
• The result: Reducing hippocampal Kcr levels impaired memory, while increasing Kcr via crotonate enhanced long-term memory, linked to crotonate-facilitated activation of glutamate-signaling genes and strengthened glutamatergic signaling with effects on presynaptic glutamate release and neuronal activity.