Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus

Activity-driven transcription plays an important role in many brain processes, including those underlying memory and epilepsy. Here, we combine genetic tagging of nuclei and ribosomes with RNA-seq, ChIP-seq, ATAC-seq and Hi-C to investigate transcriptional and chromatin changes occurring in mouse hippocampal excitatory neurons at different timepoints after synchronous activation during seizure and sparse activation by novel context exploration. The transcriptional burst is associated with an increase in chromatin accessibility of activity-regulated genes and enhancers, de novo binding of activity-regulated transcription factors, augmented promoter-enhancer interactions, and the formation of gene loops that bring together the TSS and TTS of induced genes and may sustain the fast re-loading of RNAPII complexes. Some chromatin occupancy changes and interactions, particularly those driven by AP1, remain long after neuronal activation and could underlie the changes in neuronal responsiveness and circuit connectivity observed in these neuroplasticity paradigms, perhaps thereby contributing to metaplasticity in the adult brain. nuRNA-seq, riboRNA-seq, ATAC-seq, ChIP-seq and HiC in mouse adult hippocampal excitatory neurons