Decoding the olfactory map: targeted transcriptomics link olfactory sensory neurons to glomeruli

Abstract

Sensory processing in vertebrate olfactory systems is organized across olfactory bulb glomeruli, wherein axons of peripheral sensory neurons expressing the same olfactory receptor co-terminate to transmit receptor-specific activity to central neurons. Understanding how receptors map to glomeruli is therefore critical to understanding olfaction. High-throughput spatial transcriptomics is a rapidly advancing field, but low-abundance olfactory receptor expression within glomeruli has previously precluded high-throughput mapping of receptors to glomeruli. Here we combined spatial sectioning along the anteroposterior, dorsoventral, and mediolateral axes with target capture enrichment sequencing to overcome low-abundance target expression. This strategy allowed us to spatially map 86% of olfactory receptors across the olfactory bulb and uncover a relationship between OR sequence and glomerular position.

Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb

“…To map OSN inputs to OB glomeruli with high sensitivity and consistency across animals, we used tetracycline transactivator-amplified expression of the Ca 2+ reporter GCaMP6s in all mature OSNs (OMP-IRES-tTA; tetO-GCaMP6s mice; see Methods). Consistent with earlier reports using the OMP-IRES-tTA driver line (Ma et al, 2014; Inagaki et al, 2020), this expression strategy did not appear to affect targeting of OSNs to their cognate glomeruli (Zhu et al, 2021). Odorant-evoked GCaMP6s signals were imaged with widefield epifluorescence across the dorsal surface of both OBs simultaneously in anesthetized mice, using artificial inhalation to ensure consistent odorant sampling (Eiting and Wachowiak, 2018).…”

“…Future studies should be able to probe response spectra for these glomeruli over even larger odorant panels, across concentrations, and chronically in the awake animal. Paired with platforms for linking functionally-identified glomeruli to their cognate ORs, such as retrograde labeling of OSNs (Oka et al, 2006; Shirasu et al, 2014; Saito et al, 2017) or spatial transcriptomics (Zhu et al, 2021; Wang et al, 2022), functionally identifying glomeruli could prove an efficient means of functionally deorphanizing and mapping mammalian ORs. Indeed, the number of functionally-identified glomeruli from our initial conservative survey exceeds the total number of OR-defined glomeruli whose functional properties have been characterized in prior studies to date (Peterlin et al, 2014; Shirasu et al, 2014; Saito et al, 2017).…”