In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.
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Decoding the olfactory map through targeted transcriptomics links murine olfactory receptors to glomeruli
Sensory processing in 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 in the mouse. Here we combined sequential 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.
more » « less- Award ID(s):
- 2014217
- NSF-PAR ID:
- 10370311
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Vertebrate olfactory receptors (OR) are directly exposed to microorganisms, such as viruses, due to their direct contact with the external environment. A previous study showed that nasal delivery of rhabdovirus IHNV (Infectious hematopoietic necrosis virus) in fish activate nasal immune responses marked by an increase of chemokine CCL19 and prostaglandin synthase expression in olfactory epithelia (OE), and infiltration of CD8+ cells in the OE. We hypothesize that nasal immune responses are activated by action potential signals generated by activated olfactory receptor (OR) neurons in the OE and olfactory bulb (OB). Moreover, this neural circuit can be traced from a specific OR cell type (crypt cell) in the nose to a specific site in the olfactory bulb. We tested our hypothesis by measuring olfactory responses to live attenuated IHNV virus by electro-olfactogram (EOG). We also visualized the IHNV neural circuit after activation of specific OR, and consequent internalization of molecular receptor and IHNV mixed with Alexa dextran 488 3000 MW. Our results showed different EOG olfactory responses to live attenuated IHNV and to the medium where the virus was grown (negative control) in rainbow trout. Olfactory responses followed a dose-response pattern typical of OR. Cross adaptation studies also showed that live attenuated IHNV activates a set of receptors different from those activated by virus-free supernatants. Recordings of the OB responses by electroencephalogram are under development. Preliminary tracings show fluorescent oval shaped OR in the apical border of the olfactory lamella (putative crypt cells) that extended to the ventral side of the olfactory bulb. This neural circuit differs from those visualized after exposure of trout OE to the food odorant serine. Combined, our results adds evidence for a new olfactory function in trout, which serves as a first layer of pathogen detection in vertebrates. Support or Funding Information This material is based upon work supported by the National Science Foundation under Grant No. 1755348 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.more » « less
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