# A high-throughput sequencing and imaging approach to understand the functional basis of olfaction

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2020 · $1,089,335

## Abstract

PROJECT SUMMARY
 We propose to develop a strategy for understanding olfactory coding by linking the molecular identity of
odorant receptors (OR) to their odor sensitivities in vivo and discovering the logic of neural circuits that process
smell. Unlike for other sensory modalities (i.e. vision, audition), it is not understood what properties of odorants
are important for olfaction, how these properties are processed by olfactory neural circuits, and how odorant
receptor genes have evolved to optimize such an encoding. The relationship between odorant structure
(chemical space), the sequence of odorant receptors, the underlying spatial-temporal patterns of activity in the
brain (neuronal space) and the perceived odor quality (perceptual space) has been elusive. An efficient
method for connecting the olfactory sensory spaces will have a paradigm-shifting effect on olfactory research.
 Our multidisciplinary approach will use cutting edge next-generation sequencing technologies (FISSEQ,
MAPseq and RNAseq) together with functional widefield fluorescence and two photon imaging in vivo to define
the functional properties of olfactory sensory neurons that express defined odorant receptors (ORs), to
discover their connections to individual glomeruli olfactory bulb (OB), second order OB output (mitral/tufted)
cells and map their projection statistics to the downstream olfactory processing brain areas. Using these tools,
we will map the identity and spatial layout of all 3,500 glomeruli in the mouse olfactory bulb according to the
OR types from which they receive inputs. We will further link the molecular identity of ORs to their glomerular
responses to hundreds of odorants (>500) in the form of OR/odorant binding affinity matrices across hundreds
of glomeruli (~500) that are optically accessible in vivo. In the same samples, we will track thousands
(>1,000/experiment) of individual olfactory bulb projections to their input glomeruli and their target brain areas
by RNA-barcoding in relation to their tuning to odorants via multiphoton imaging in vivo.
 Our approach will bridge the gap between the molecular biology of ORs and neurophysiology and will
usher in a new era of understanding the functional basis of olfaction. It will allow unprecedented resolution and
throughput for determining OR-ligand interactions across hundreds of odorants, and the connectivity of tens of
thousands of single neurons at once in a single specimen. The data obtained will enable the study of OR-
ligand interactions, relate the chemical identity of odorants to olfactory perception, and the construction of
artificial nose devices for immediate biomedical applications, including disease diagnostics.

## Key facts

- **NIH application ID:** 9996339
- **Project number:** 5R01DC017876-03
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Dinu Florentin ALBEANU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,089,335
- **Award type:** 5
- **Project period:** 2018-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996339

## Citation

> US National Institutes of Health, RePORTER application 9996339, A high-throughput sequencing and imaging approach to understand the functional basis of olfaction (5R01DC017876-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996339. Licensed CC0.

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