Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

• Published in: bioRxiv
• Main Authors: Soelter, Jan, Schumacher, Jan, Spors, Hartwig, Schmuker, Michael
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.09.2019
• Subjects: Aroma compounds; Artificial intelligence; Computer applications; Embedding; Learning algorithms; Machine learning; Olfaction; Olfactory bulb; Olfactory glomeruli; Smell; Statistical analysis; Structure-activity relationships
• DOI: 10.1101/489666

Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli innervated by the MOR18-2 olfactory receptor in the dorsal olfactory bulb (dOB). Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We discovered several previously unknown odorants activating MOR18-2 glomeruli, and we obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Physico-chemical MRR descriptions revealed that the spatial layout of glomeruli followed a chemical logic. Our results confirm earlier findings that demonstrate a partial chemical map underlying glomerular arrangement in the dOB. Moreover, our novel methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction. Footnotes * Section "Results/Tunotopic Embedding": We quantified the relation between distances of in-patch glomeruli to MOR18-2 and distances of out-of-patch glomeruli to MOR18-2 and found that in-patch glomeruli were closer to MOR18-2 (Mann-Whitney U statistics, p<10-5). The manuscript has been updated accordingly. We also quantified the alignment of "superclusters" along the lateral-posterior/medial-anterior axis and performed a shuffle analysis to verify that this orientation is not a result of chance. Section Results/Chemotopic embedding: We performed an additional analysis that quantifies the chemical similarity of glomerular receptive fields with respect to their spatial proximity to MOR18-2, in-cluding a shuffled control. These confirmed our qualitative observation that the receptive fields of glomeruli in spatial proximity to MOR18-2 are more likely to chemically similar to MOR18-2's MRR. The manuscript has been updated accordingly. In addition, several minor corrections in phrasing for clarity and spelling. The supplement has been updated with three new figures (S4, S5, S6) corresponding to the new quantitative analysis.