Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2

Abstract

Summary: RNA localization is one mechanism neurons use to spatially and temporally regulate gene expression at synapses. Here, we test the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discover that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we describe more than 1,000 differentially expressed dendritic RNAs, suggesting that RNA localization and local translation are regulated in a cell type-specific manner. Furthermore, by focusing Gene Ontology analyses on the plasticity-resistant CA2, we identify an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways differentially influence plasticity and mitochondrial respiration in CA2. These data indicate that differences in dendritic transcriptomes may regulate cell type-specific properties important for learning and memory and may influence region-specific differences in disease pathology. : RNA localization provides spatial and temporal control over protein expression at synapses. Farris et al. show that hippocampal subregions, areas important for memory, localize distinct subsets of RNAs to dendrites, uncovering an additional layer of cell-specific regulation. Focusing on CA2 dendrites, they identify mitochondria as a regulator of CA2 plasticity. Keywords: hippocampal CA2, dendritic RNA, RNA localization, mitochondria, calcium buffering, local translation, alternative splicing