Olfactory Detection Thresholds for Primary Aliphatic Alcohols in Mice

Abstract

<jats:title>Abstract</jats:title> <jats:p>Probing the neural mechanisms that underlie each sensory system requires the presentation of perceptually appropriate stimulus concentrations. This is particularly relevant in the olfactory system as additional odorant receptors typically respond with increasing stimulus concentrations. Thus, perceptual measures of olfactory sensitivity provide an important guide for functional experiments. This study focuses on aliphatic alcohols because they are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination and assess odor-structure activity relationships in mice. However, despite their frequent use, a systematic study of the relative sensitivity of these odorants in mice is not available. Thus, we assayed the ability of C57BL/6J mice to detect a homologous series of primary aliphatic alcohols (1-propanol to 1-heptanol) using a head-fixed Go / No-Go operant conditioning assay combined with highly reproducible stimulus delivery. To aid in the accessibility of our data, we report the animal’s threshold to each odorant according to the 1) ideal gas condition, 2) non-ideal gas condition (factoring in the activity of the odorant in the solvent), and 3) the liquid dilution of the odorant in the olfactometer. Of the odorants tested, mice were most sensitive to 1-hexanol and least sensitive to 1-butanol. These updated measures of murine sensitivity will hopefully guide experimenters in choosing appropriate stimulus concentrations for experiments using these odorants.</jats:p>

Using Head-Mounted Ethanol Sensors to Monitor Olfactory Information and Determine Behavioral Changes Associated with Ethanol-Plume Contact during Mouse Odor-Guided Navigation

“…By following our paradigm for oxide sensors that are sensitive to other compounds, this method could be applied to other odors. A recent publication by Williams and Dewan (2020) has reported detection thresholds of mice for aliphatic alcohols about 3 orders of magnitude smaller than the sensitivity of the alcohols sensors, which is in the parts per million range, used here. However, under the conditions of turbulent transport (Celani et al, 2014) employed in our study, odor is transported as high concentration packets (whiffs) interspersed with periods of no odor (blanks).…”

“…However, under the conditions of turbulent transport (Celani et al, 2014) employed in our study, odor is transported as high concentration packets (whiffs) interspersed with periods of no odor (blanks). Reaching low concentrations on the scale of the thresholds presented by Williams and Dewan (2020) would occur via diffusion, taking place over larger spatial and temporal scales than in our laboratory setting. Another problem that we encountered during experiments with freely behaving animals is tether management within a large, top-sealed wind tunnel.…”

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

“…We note that the concentrations used here were comparable to or higher than psychophysical detection thresholds measured with rigorous behavioral assays in mice (Dewan et al, 2018;Cichy et al, 2019;Williams and Dewan, 2020), suggesting that the sparse responses at these concentrations can support odor perception.…”

“…Rather than deliver odorants at a single arbitrarily- or empirically-chosen concentration, we used a rational search strategy that allowed adjusting the concentration of each odorant across a >1000-fold (sub-pico-to nanomolar) range in order to identify high-sensitivity odorant-glomerulus interactions and to, ideally, pair each glomerulus with its primary odorant. Guided by recent studies indicating mouse perceptual thresholds in the picomolar range for at least some odorants (Dewan et al, 2018; Williams and Dewan, 2020), we initially set estimated delivered odorant concentrations to ~1 pM (see Methods). Across a series of pilot experiments, concentrations were then systematically increased (or occasionally decreased) by tenfold steps up to ~1 nM to identify the lowest concentration for each odorant capable of reliably activating at least one glomerulus, with responses averaged across at least three trials (typically, four) per concentration and odorant.…”

Probing Olfaction in Space and Time

“…In rodents, the sense of smell has evolved to be exquisitely sensitive. Mice have been trained in the laboratory to reliably detect one in 1 billion molecules (Williams and Dewan, 2020). How can the nervous system perform such sensitive detection and what determines perceptual detection thresholds?…”