Mice lacking NKCC1 have normal olfactory sensitivity

Abstract

When olfactory receptor neurons respond to odors, a depolarizing Cl(-) efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl(-) against an electrochemical gradient. In isolated olfactory receptor neurons, the Na(+)+K(+)+2Cl(-) cotransporter NKCC1 is essential for Cl(-) accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. To determine whether NKCC1 is required for normal olfactory sensitivity, olfactory sensitivity was compared between knockout (KO) mice carrying a null mutation for NKCC1 and wild-type (WT) littermates. Using operant behavioral techniques, olfactory sensitivity was measured using a commercial liquid-dilution olfactometer. Detection thresholds for the simple odorants cineole, 1-heptanol, and 1-propanol were compared in KO and WT animals. Regardless of the stimulus conditions employed, no systematic differences in behavioral thresholds were evident between KO and WT animals. We conclude that NKCC1 is not required for normal olfactory sensitivity.

Fig. 1

Number of trial blocks to criterion for the odorant discrimination task. Number of trial blocks required to reach an initial discrimination criterion of 85% for a group of WT (n = 3) and KO (n = 6) mice for two different odorants (cineole and 1-propanol).

Fig. 2

Response accuracy of WT and KO mice in detection of serial dilutions of 1-propanol. Means are shown for 2 WT mice and 3 KO mice. For each animal, each data point is the average of three successive blocks of 20 trials (10 S+ and 10 S−, presented randomly) once the criterion of 85% on three successive blocks was attained. Testing was continued for a maximum of five sessions at a given dilution. Concentrations represent the fraction of 1-propanol by volume in the liquid phase within the saturation bottle. Threshold was the last dilution at which an animal reached the 85% criterion. Bars represent the full range of values for each point. Bars on the left side of each point are from WT mice; bars to the right are from KO mice. Dashed lines are shown at 50% (expected chance performance) and 85% (criterion for stimulus detection).

Fig. 3

Response accuracy of a WT mouse and a KO mouse in detection of serial dilutions of 1-heptanol (A) or cineole (B). Each data point is the average of three successive blocks of 20 trials (10 S+ and 10 S−, presented randomly) once the criterion of 85% on three successive blocks was attained. Testing was continued for a maximum of two sessions at a given dilution. Concentrations represent the fraction of odorant by volume in the liquid phase within the saturation bottle. Threshold concentrations for the WT mice were 10⁻² (1-heptanol, A) and 5 × 10⁻⁵ (cineole, B). Threshold concentrations for the KO mice were 10⁻² (1-heptanol, A) and 10⁻³ (cineole, B). Dashed lines are shown at 50% (expected chance performance) and 85% (criterion for stimulus detection).