An Olfactory Subsystem that Detects Carbon Disulfide and Mediates Food-Related Social Learning

Abstract

Summary Olfactory signals influence social interactions in a variety of species [1, 2]. In mammals, pheromones and other social cues can promote mating or aggression behaviors, can communicate information about social hierarchies, genetic identity and health status, and can contribute to associative learning [1–5]. However, the molecular, cellular and neural mechanisms underlying many olfactory-mediated social interactions remain poorly understood. Here, we report that a specialized olfactory subsystem that includes olfactory sensory neurons (OSNs) expressing the receptor guanylyl cyclase GC-D, the cyclic nucleotide-gated channel subunit CNGA3 and the carbonic anhydrase isoform CAII (GC-D+ OSNs) [6–11] is required for the acquisition of socially transmitted food preferences (STFPs) in mice. Using electrophysiological recordings from gene-targeted mice, we show that GC-D+ OSNs are highly sensitive to the volatile semiochemical carbon disulfide (CS2), a component of rodent breath and a known social signal mediating the acquisition of STFPs [12–14]. Responses to sub-micromolar concentrations of CS2 in the main olfactory epithelium or in identified GC-D+ OSNs are absent in mice lacking CNGA3 or CAII and drastically reduced in mice lacking GC-D. Mice in which GC-D+ OSN transduction mechanisms have been disrupted fail to acquire STFPs from either live or surrogate demonstrator mice and do not exhibit neuronal activation of the ventral subiculum of the hippocampus, a brain region implicated in STFP retrieval [15]. Our findings indicate that GC-D+ OSNs detect chemosignals that facilitate food-related social interactions.

The wiring of Grueneberg ganglion axons is dependent on neuropilin 1

“…This type of wiring is unlike the canonical projection pattern observed in the main olfactory system, but is reminiscent of the one found in the vomeronasal system, where the numerous like glomeruli are often linked together, and is very similar to the one corresponding to GC-D-expressing neurons. Knowing that both vomeronasal and GC-D neurons are specialized in interpreting innate and/or socially relevant signals (Halpern and MartinezMarcos, 2003;Munger et al, 2010), it naturally suggests that Grueneberg neurons play a role in inter-individual interactions.…”

“…1A). This necklace-shaped group of glomeruli is also innervated by sensory neurons located in the main olfactory system, which detect a variety of semiochemicals (Hu et al, 2007;Leinders-Zufall et al, 2007;Munger et al, 2010). Whether specific necklace glomeruli are co-innervated by Grueneberg and main olfactory projections is unknown.…”

Differential Effects of Dopamine Receptor D1-Type and D2-Type Antagonists and Phase of the Estrous Cycle on Social Learning of Food Preferences, Feeding, and Social Interactions in Mice

“…In this paradigm, social learning is observed when, during a brief interaction with a conspecific who has just eaten a novel diet, an 'observer' (OBS) can acquire olfactory information about food eaten by a conspecific 'demonstrator' (DEM) by sniffing the DEM's mouth area . Specific neurons in the olfactory system (Munger et al, 2010) detect carbon disulfide, a semiochemical product of digestion needed for the social learning of a food preference Heyes and Durlach, 1990), so investigation of the DEM's mouth area is critical for STFP in rats (Galef and Stein, 1985) and mice (Valsecchi and Galef, 1989).…”

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

“…Nevertheless, the number of sensory neurons responsive to CO 2 is unusual and suggests that worms can integrate the detection of CO 2 and other cues at the earliest stages of sensory processing. Analogously, olfactory neurons in mice that respond to CO 2 are also exquisitely sensitive to the peptide hormones uroguanylin and guanylin, natural urine stimuli, as well as the volatile semiochemical carbon disulfide (64,65). These sensors are different from the olfactory sensors initially identified in the fly that respond only (or primarily) to CO 2 stimuli (66), and this finding suggests that both worms and mice can couple the detection of CO 2 to that of other sensory cues within multimodal neurons, perhaps as an efficient strategy to glean information from a generic cue such as CO 2 (67).…”