Reconstruction of the mouse olfactory glomerular map using single-cell technologies

Oral presentation

I-Hao Wang ¹, Evan Murray ^{2, 9}, Gregory Andrews ^{3, 9}, Elisa Donnard ^{3, 9}, Violeta DuranLaforet ⁴, Hao-Ching Jiang ¹, SungJin Park ¹, Daniel Bear ^{5, 6}, Dorothy Schafer ⁴, Manuel Garber ³, Zhiping Weng ³, Fei Chen ^{2, 7}, Evan Macosko ^{2, 8}, Paul Greer ¹

¹ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA, ² Broad Institute of Harvard and MIT, Cambridge, MA, USA, ³ Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA, ⁴ Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA, ⁵ Department of Psychology, Stanford University, Stanford, CA, USA, ⁶ Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA, ⁷ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA, ⁸ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA, ⁹ These authors contributed equally

The olfactory system's ability to detect and discriminate between the vast array of chemicals present in the environment is critical for an animal to be able to forage food, find mates, and avoid predation. In mice, these chemicals are detected by odorant receptor (OR) proteins that are expressed by olfactory sensory neurons (OSNs). Each OSN expresses only one OR, and all OSNs that express the same OR project their axons to a stereotyped position within the olfactory bulb to form a glomerulus. This organization results in a given odorant triggering a unique, but spatially invariant, pattern of glomerular activation, and it is believed that this organization may be critical for assisting the brain in decoding odor identity. However, a major impediment to understanding the computation that transforms patterns of glomerular activity to the decoding of odor identity, is that the positions of only a handful of glomeruli are known. Here, we use spatial transcriptomics and machine learning to reconstruct a map of the majority of glomerular positions within the mouse olfactory bulb. Using single cell RNA sequencing, we find that each type of OSN expresses a unique transcriptional program—beyond simply the OR that is has chosen—that distinguishes it from all other OSNs. These unique transcriptional programs are highlighted by a subset of axon guidance genes, and together are sufficient to predict where within the olfactory bulb the OSN will form its glomerulus. Intriguingly, the transcriptional program of a given OSN is tightly linked to the properties of the OR that it displays, which results in glomeruli that respond to similar odorants being in close proximity to one another. Together, these results provide a new, mostly complete map of glomerular positioning within the mouse olfactory bulb.