Temporal integration in nasal lateralization of homologous alcohols

Abstract

Through temporal integration, sensory systems accumulate stimulus energy, e.g., photons, acoustic energy, or molecules, over time to detect weaker signals than they otherwise could. Past studies found imperfect temporal integration in detection of nasal irritation: To maintain a fixed level of detection, one must increase stimulus duration by more than twofold to compensate for cutting concentration in half. Despite this generality, integration varied widely among compounds, from nearly perfect, i.e., an increase in duration of slightly more than twofold could compensate for cutting concentration in half, to highly imperfect. How do such differences relate to molecular parameters? Perhaps molecules that more readily dissolve into the lipid-rich perireceptor environment will accumulate, and therefore integrate, better over time. To test this hypothesis, studies compared temporal integration for three compounds that differ systematically in lipid solubility: n-ethanol, n-butanol, and n-hexanol. Subjects were healthy, adult humans. Nasal lateralization was used to measure irritation threshold. Subjects received a fixed concentration of a single compound within each experimental session, and stimulus duration was varied to find the briefest stimulus subjects could reliably lateralize. Concentration and compound varied across sessions. Consistent with the hypothesis, integration did become closer to perfect as lipid solubility increased. That just one molecular parameter can help predict degree of integration suggests that a structure-activity approach to understanding temporal integration shows promise.

Fig. 1

Simplified schematic of the olfactometer. The diagram illustrates channels for one nostril only. The full olfactometer includes two sets of the parts pictured. MC = glass mixing chamber, and SV = three-way, Teflon® solenoid valve. Tubing that carries flow from the room (vent) is illustrated by dashed lines. Tubing that carries flow toward the nose is illustrated by solid lines. Arrow-heads indicate direction of airflow. Rotameters (not shown) controlled flow-rate in all channels. “Background,” “target,” and “blank” are defined in the text.

Fig. 2

Threshold stimulus-duration (log ms) vs. concentration of VOC (log ppm) for ethanol, butanol, and hexanol. Error bars represent 95% confidence intervals (upper and lower error bars are asymmetric due to the logarithmic transform). The dashed lines have a slope if -1, i.e., predictions for perfect integration (see text). Solid lines represent linear functions fit to data using least-squares regression. equations. A) Data for ethanol. Best fit linear equation: LogT = -2.75LogC + 12.50, R² = .98, where “T” represents duration threshold and “C” represents concentration. B) Data for butanol, LogT = -1.90LogC + 8.69, R² = .99. C) Data for hexanol, LogT = -1.26LogC + 4.07, R² = .98.