Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]

RNA localization is one mechanism that neurons use to spatially and temporally regulate gene expression at synapses. Here, we tested the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discovered that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we uncovered a surprising number of cell type and compartment specific differences in RNA expression and alternative splicing, some of which pointed to differences within interneuron and non-neuronal cells present in dendritic laminae. Further, by focusing gene-ontology analyses on the plasticity-resistant CA2, we identified an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways influence plasticity and mitochondrial respiration in CA2. In sum, our results support accumulating evidence that thousands of RNAs are present in adult dendrites that likely function to regulate cell type specific processes in dendrites. Overall design: Hippocampal cell-type and compartment specific transcriptomes were generated using laser capture microdissection on three adult male Amigo2-EGFP mice. The cell body (stratum pyramidale and granule cell layer) and dendritic layers (stratum radiatum and molecular layer) from CA1, CA2, CA3 and DG were multiplexed per mouse (8 regions per mouse) and each sequenced on an Illumina NextSeq500 instrument.