Hippocampal single-nucleus sequencing identifies a unique transcriptional signature that is predictive of reactivity in dentate granule neurons

Neuronal circuits are constantly remodeled in response to activity, but the extent and the specificity of activity-induced transcription are unknown. In this study, we used single nucleus RNA-seq to compare transcriptional responses to activity throughout the hippocampus following exposure to a novel environment. By comparing activated and non-activated nuclei, we found that dentate granule cells (DGCs) have a unique transcriptional response to activity that differs in both magnitude and quality compared to CA1 pyramidal cells and vasoactive intestinal polypeptide (VIP) interneurons. We further used single nuclei RNA-seq to compare transcriptional responses to activity throughout the dentate gyrus following exposure to two contexts and identified that DGCs generate a transcriptional signature that is predictive of reactivity. Single-nucleus RNA-seq of mouse hippocampal neurons after exposure to a novel experience or remaining in the home cage and stained for cell type-specific markers, NEUN, PROX1 and CTIP2 as well as the activity-dependent marker FOS. In addition, single-nucleus RNA-seq of mouse DG neurons after exposure to two separate contexts stained for cell type-specific markers, PROX1 and CTIP2, as well as two temporally distinct activity-dependent markers, FOS and ARC.