Single cell RNAseq of mouse olfactory bulb reveals cellular heterogeneity and activity dependent molecular census of adult-born neurons

Cellular heterogeneity within the mammalian brain poses a challenge towards understanding its complex functions. Within the olfactory bulb (OB), odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality is influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity, and to better understand the developmental programs of adult-born neurons, we utilized single cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and non-neuronal cell types. We also analyzed molecular changes during adult-born interneuron maturation, and uncovered developmental programs within their gene expression profiles. Finally, we discovered that distinct neuronal subtypes are differentially affected by sensory experience. Together, these data provide a transcriptome-based foundation for investigating subtype-specific neuronal function in the OB, charting the molecular profiles that arise during the maturation and integration of adult-born neurons, and documenting activity-dependent changes in the cellular composition of the olfactory system. To develop a comprehensive profile of cellular heterogeneity within the OB, here we employed high-throughput single-cell RNA sequencing (scRNA-seq) (Zheng et al. 2017) of activity manipulated and wildtype mouse olfactory bulbs. This technique allows an in-depth categorization of single cell molecular signatures, and provides an analysis of potential developmental and activity-dependent changes that occur in adult-born neuron populations. Together, our data inform the heterogeneity of interneurons within the OB, provide a molecular blueprint of stereotyped developmental programs for OB interneurons, and reveal the transcriptional changes that govern activity-dependent circuit integration of adult-born neurons. Furthermore, our results suggest that distinct molecular mechanisms act on different subsets of adult-born neurons, driving diversity and survival of adult-born interneuron subsets in an activity-dependent manner.