The receptor guanylyl cyclase type D (GC-D) ligand uroguanylin promotes the acquisition of food preferences in mice

Abstract

Rodents rely on olfactory stimuli to communicate information between conspecifics that is critical for health and survival. For example, rodents that detect a food odor simultaneously with the social odor carbon disulfide (CS(2)) will acquire a preference for that food. Disruption of the chemosensory transduction cascade in CS(2-)sensitive olfactory sensory neurons (OSNs) that express the receptor guanylyl cyclase type D (GC-D; GC-D+ OSNs) will prevent mice from acquiring these preferences. GC-D+ OSNs also respond to the natriuretic peptide uroguanylin, which is excreted into urine and feces. We analyzed if uroguanylin could also act as a social stimulus to promote the acquisition of food preferences. We found that feces of mice that had eaten odored food, but not unodored food, promoted a strong preference for that food in mice exposed to the feces. Olfactory exploration of uroguanylin presented with a food odor similarly produced a preference that was absent when mice were exposed to the food odor alone. Finally, the acquisition of this preference was dependent on GC-D+ OSNs, as mice lacking GC-D (Gucy2d(-)(/-) mice) showed no preference for the demonstrated food. Together with our previous findings, these results demonstrate that the diverse activators of GC-D+ OSNs elicit a common behavioral result and suggest that this specialized olfactory subsystem acts as a labeled line for a type of associative olfactory learning.

Keywords: natriuretic peptide; olfaction; olfactory subsystem; social learning.

Figure 1

Preference testing with feces. (A) C57BL/6J demonstrator (De) mice eat regular chow (grey) or chow with added odor (cocoa or cinnamon; black). (B) Feces are collected from each demonstrator mouse. (C) Observer (Ob) mice explore feces from the demonstrators. (D) Observer mice are then given the choice of 2 foods: 1 odored with cinnamon and 1 odored with cocoa.

Figure 2

Preference testing with uroguanylin. (A) Observer (Ob) mice (either C57BL/6J or Gucy2d ^+/− and Gucy2d ^−/−) explore saline containing a food odor (cocoa or cinnamon) and 50μM or 50nM uroguanylin (UG; black) or the food odor alone (grey). (B) Observer mice are then given the choice of 2 foods: 1 odored with cinnamon and 1 odored with cocoa.

Figure 3

Feces contain chemostimuli that promote the acquisition of food preferences. C57BL/6J mice exposed to feces obtained from mice that consumed odored (cinnamon or cocoa) food show a significant preference (PR = demonstrated food consumed/total food consumed) for food containing that same odor (Z-test, z =5.74, P = 0.02). Mice exposed to feces obtained from mice that consumed food with no added odor showed no preference for cinnamon- or cocoa-odored food (Z-test, z = 0.50, P = 0.44). *1-way ANOVA F(1,14) = 8.61, P < 0.05. Error bars, standard error of the mean.

Figure 4

Uroguanylin promotes the acquisition of food preferences. C57BL/6J mice exposed to a food odor (cinnamon or cocoa) plus uroguanylin show a significant preference (PR = demonstrated food consumed/total food consumed) for food containing that same odor (50nM uroguanylin: Z-test, z = 6.87, P = 0.008; 50 μM uroguanylin: Z-test, z = 6.72, P = 0.009). Mice exposed to the food odor alone showed no preference for cinnamon- or cocoa-odored food (Z-test, z = 0.61, P = 0.41). 1-way ANOVA: F(2,21) = 9.491, P < 0.01. *Dunnett post-hoc, P < 0.01. Error bars, standard error of the mean.

Figure 5

GC-D is required for the acquisition of food preferences in response to uroguanylin. Gucy2d ^+/− mice exposed to a food odor (cinnamon or cocoa) plus uroguanylin show a significant preference (PR = demonstrated food consumed/total food consumed) for food containing that same odor (50nM uroguanylin: Z-test, z = 5.40, P = 0.03; 50 μM uroguanylin: Z-test, z = 9.47, P = 0.0004). Gucy2d ^−/− mice exposed to a food odor (cinnamon or cocoa) plus uroguanylin showed no preference for cinnamon- or cocoa-odored food (50nM uroguanylin: Z-test, z = 0.94, P = 0.37; 50 μM uroguanylin: Z-test, z = 0.27, P = 0.46). 2-way ANOVA: uroguanylin concentration, F(1,28) = 0.47, P = 0.42; *Genotype, F(1,28) = 45.57, P < 0.0001; uroguanylin concentration × genotype, F(1,28) = 2.23, P = 0.09. Error bars, standard error of the mean.