Altered sexual and social behaviors in trp2 mutant mice

Abstract

We have used gene targeting to generate mice with a homozygous deficiency in trp2, a cation channel expressed in the vomeronasal organ (VNO). Trp2 mutant animals reveal a striking reduction in the electrophysiological response to pheromones in the VNO, suggesting that trp2 plays a central role in mediating the pheromone response. These mutants therefore afford the opportunity to examine the role of the VNO in the generation of innate sexual and social behaviors in mice. Trp2 mutant males and nursing females are docile and fail to initiate aggressive attacks on intruder males. Male-female sexual behavior appears normal, but trp2 mutant males also vigorously mount other males. These results suggest that the cation channel trp2 is required in the VNO to detect male-specific pheromones that elicit aggressive behaviors and dictate the choice of sexual partners.A nimals exhibit behavioral repertoires that are often innate and result in stereotyped sexual and social responses to their environment. Innate behaviors do not require learning or experience and are likely to reflect the activation of developmentally programmed neural circuits. The appropriate expression of an innate behavioral array frequently requires signals from the outside world. Mice rely heavily on olfactory information to sense their environment. In mice, odorants are recognized by two anatomically and functionally distinct sensory organs, the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) (1, 2). The main olfactory epithelium is thought to recognize odors that provide information about the world at large and can result in measured behavioral responses. In contrast, the VNO has traditionally been implicated in the recognition of pheromones, odorants that provide information about the social and sexual status of other individuals within the species (3, 4). Activation of the VNO is thought to result in innate neuroendocrine and behavioral responses.In mammals, the chemical nature of the pheromones that activate the VNO to elicit innate behavioral responses has not been elucidated (5). Moreover, it has been difficult to sort out the relative roles of the MOE and the VNO in mediating specific behaviors. In male hamsters, removal of the olfactory bulb, which receives input from both the MOE and the VNO, abolishes the sexual response (6). Removal of the VNO alone diminishes the robustness of the male mating response, but does not eliminate sexual behavior (7). The consequence of VNO removal is most apparent in sexually naive animals, suggesting that with experience the main olfactory system assumes an increasingly important role in the sexual response (8, 9). Other innate behaviors, including lordosis in female pigs (10) in response to the male hormone, androstenone, or suckling behavior in newborn rabbits (11) in response to mammary secretions, are unaffected by removal of the VNO. These innate behavioral responses are likely to be elicited by pheromones that activate the main olfactory system. Thus, mammals have evolved innate behavioral ...

The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

“…In addition, MOE responses to MHC peptides are inhibited by adenylcyclase antagonists and critically depend on a functional CNGA4 gene, which encodes a principal subunit of a cyclic AMP-sensitive CNG channel expressed in MOE but not in the VNO, thus showing that MHC peptides ligands are transduced in the MOE by cells employing a cAMP-signaling pathway and the olfactory CNG channel. Similar results have been obtained with the odorant 2-heptanone: its detection appears to be dependent on the Trp2 gene in the VNO, while in the MOE, detection of 2-heptanone depends on the CNGA2 [60,63]. At the behavioral level, this processing of the same olfactory signals is not just a redundancy.…”

“…Despite this convergent body of results, a role for the VNO in mate recognition has been recently claimed by studies using transient receptor potential cation 2 channel knock-out male mice [60,105]. Indeed, deletion of Trp2 results in a dramatic reduction of various electrophysiological responses in VNO sensory neurons after exposure to urinary odorants.…”

“…Indeed, deletion of Trp2 results in a dramatic reduction of various electrophysiological responses in VNO sensory neurons after exposure to urinary odorants. In addition, at the behavioral level, Trp2-KO male mice mounted male and female subjects indiscriminately [60,105], leading to the conclusion that the VNO is required for sex discrimination. However neither study measured olfactory sex discrimination directly.…”

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

“…Since maternal aggression is severely reduced in mutant mice having olfactory (Cnag2 -/y , Mandiyan et al, 2005; AC3 -/-, Wang and Storm, 2011) or vomeronasal dysfunction (Leypold et al, 2002;Kimchi et al, 2007;Hasen and Gammie, 2009;Chamero et al, 2011;Leinders-Zufall et al, 2014), it seems likely that exposure to pup chemosignals detected by both the olfactory and vomeronasal epithelia is necessary for the induction of maternal aggression. However, our results indicate that virgin females that have been continuously exposed to pups for 3-4 days show negligible aggressive behaviour towards intruders approaching the nest (from which pups had been previously…”

“…When lactating females are used in maternal aggression tests, nest defence is also clearly impaired in trpc2 -/-mutants (Leypold et al, 2002;Kimchi et al, 2007) even when the mutation is shifted into a line of mice selected for their robust maternal aggression (Hasen and Gammie, 2009). This indicates that vomeronasal stimuli elicit both intermale and maternal aggression.…”