Pheromone Detection in Male Mice Depends on Signaling through the Type 3 Adenylyl Cyclase in the Main Olfactory Epithelium

Wang, Zhenshan; Sindreu, Carlos; Li, Vicky; Nudelman, Aaron S.; Chan, Guy C.‐K.; Storm, Daniel R.

doi:10.1523/jneurosci.1967-06.2006

Cited by 131 publications

(132 citation statements)

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“…olfactory rather than vomeronasal stimuli, with attractive properties for females. Thus, farnesenes and other volatile vomeronasal ligands stimulate the olfactory epithelium (Wang et al, 2006). Lin et al (2005) combined gas chromatography with simultaneous recording of the activity of mitral cells in the main olfactory bulb stimulated by individual volatiles in mouse urine.…”

Section: A Volatile Male Sexual Pheromones: Chemical Species and Thementioning

confidence: 99%

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

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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From sexual attraction to maternal aggression: When pheromones change their behavioural significance, Hormones and Behavior (2014), doi: 10.1016/j.yhbeh.2014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractThis paper reviews the role of chemosignals in the socio-sexual interactions of female mice, and reports two experiments testing the role of pup-derived chemosignals and the male sexual pheromone darcin in inducing and promoting maternal aggression. Female mice are attracted to urine-borne male pheromones. Volatile and non-volatile urine fractions have been proposed to contain olfactory and vomeronasal pheromones. In particular, the male-specific major urinary protein (MUP) MUP20, darcin, has been shown to be rewarding and attractive to females. Non-urinary male chemosignals, such as the lacrimal protein ESP1, promote lordosis in female mice, but its attractive properties are still to be tested. There is evidence indicating that ESP1 and MUPs are detected by vomeronasal type 2 receptors (V2R).When a female mouse becomes pregnant, she undergoes dramatic changes in her physiology and behaviour. She builds a nest for her pups and takes care of them. Dams also defend the nest against conspecific intruders, attacking especially gonadally intact males. Maternal behaviour is dependent on a functional olfactory system, thus suggesting a role of chemosignals in the development of maternal behaviour. Our first experiment demonstrates, however, that pup chemosignals are not sufficient to induce maternal aggression in virgin females. In addition, it is known that vomeronasal stimuli are needed for maternal aggression.Since MUPs (and other molecules) are able to promote intermale aggression, in our second experiment we test if the attractive MUP darcin also promotes attacks on castrated male intruders by lactating dams. Our findings demonstrate that the same chemosignal, darcin, promotes attraction or aggression according to female reproductive state.

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Section: A Volatile Male Sexual Pheromones: Chemical Species and Thementioning

confidence: 99%

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

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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“…In these experiments in which the MOE was ablated, the function of the VNS is not directly disrupted, because the VNS is activated by direct application of urine to the nostril. Thus, these results indicate that the MOS also contributes to pheromone processing and related behaviors.Nonconditional disruption of genes encoding signal transduction proteins that are required for activation of olfactory neurons, such as cyclic nucleotide-gated channel (Cnga2) or adenylyl cyclase 3, impairs several social behaviors (11,(13)(14)(15). However, complete loss of MOS function causes anosmia and severely impairs sniffing and chemoinvestigatory behaviors (11,13,14,16).…”

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confidence: 99%

“…However, complete loss of MOS function causes anosmia and severely impairs sniffing and chemoinvestigatory behaviors (11,13,14,16). Chemoinvestigation and the accompanying physical contact of the nose and pheromone source are essential for VNS activation; therefore, the loss of MOS function indirectly impairs the VNS, because the VNS becomes behaviorally isolated from pheromone cues in mice (16)(17)(18)(19).…”

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confidence: 99%

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Matsuo¹,

Hattori

Asaba

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.social behavior | pheromone processing | main olfactory system | vomeronasal system M ost mammals have two major olfactory subsystems-the main olfactory system (MOS) and vomeronasal system (VNS). The MOS comprises the main olfactory epithelium (MOE), in which olfactory sensory neurons detect odorants, and their projection target, the main olfactory bulb (MOB) (Fig. S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1-8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9, 10). In mice, chemical ablation of the MOE impairs male and female sexual behaviors (11,12). In these experiments in which the MOE was ablated, the function of the VNS is not directly disrupted, because the VNS is activated by direct application of urine to the nostril. Thus, these results indicate that the MOS also contributes to pheromone processing and related behaviors.Nonconditional disruption of genes encoding signal transduction proteins that are required for activation of olfactory neurons, such as cyclic nucleotide-gated channel (Cnga2) or adenylyl cyclase 3, impairs several social behaviors (11,(13)(14)(15). However, complete loss of MOS function causes a...

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“…Thus, it now is clear that the main olfactory system is involved in detection of semiochemicals and that the cAMP signaling pathway plays an important role in signal transduction for certain pheromones and MHC peptides (16,(19)(20)(21). However, the potential involvement of other signaling pathways is not fully understood (21,22).Previously, we demonstrated that genetic elimination of subunit A2 of the CNG channel, which disrupts the canonical cAMP pathway, significantly reduced but did not eliminate physiological and behavioral responses to pheromones in the main olfactory system (22). The transduction pathway responsible for these responses was not identified, but pharmacological experiments suggested involvement of phospholipase C (PLC).…”

mentioning

confidence: 99%

“…Further, a class of chemosensory receptors that recognize social amines found in urine have been identified recently in the MOE (18). Thus, it now is clear that the main olfactory system is involved in detection of semiochemicals and that the cAMP signaling pathway plays an important role in signal transduction for certain pheromones and MHC peptides (16,(19)(20)(21). However, the potential involvement of other signaling pathways is not fully understood (21,22).…”

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confidence: 99%

Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

Lin

Margolskee

Donnert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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157

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Olfactory sensory neurons (OSNs) in the main olfactory epithelium respond to environmental odorants. Recent studies reveal that these OSNs also respond to semiochemicals such as pheromones and that main olfactory input modulates animal reproduction, but the transduction mechanism for these chemosignals is not fully understood. Previously, we determined that responses to putative pheromones in the main olfactory system were reduced but not eliminated in mice defective for the canonical cAMP transduction pathway, and we suggested, on the basis of pharmacology, an involvement of phospholipase C. In the present study, we find that a downstream signaling component of the phospholipase C pathway, the transient receptor potential channel M5 (TRPM5), is coexpressed with the cyclic nucleotide-gated channel subunit A2 in a subset of mature OSNs. These neurons project axons primarily to the ventral olfactory bulb, where information from urine and other socially relevant signals is processed. We find that these chemosignals activate a subset of glomeruli targeted by TRPM5-expressing OSNs. Our data indicate that TRPM5-expressing OSNs that project axons to glomeruli in the ventral area of the main olfactory bulb are involved in processing of information from semiochemicals.signal transduction ͉ pheromone ͉ stimulated emission depletion (STED) microscopy T he olfactory system perceives not only odorants that convey information on the environment but also semiochemicals (chemicals involved in animal communication, from the Greek semeion for ''sign''), including pheromones (1-4). A key step in transmission of information is activation of the canonical cAMP signaling pathway by binding of odorants to olfactory receptors, resulting in influx of Ca 2ϩ through a cyclic nucleotide-gated (CNG) channel and subsequent depolarization (5, 6). Targeted disruption of elements of the cAMP pathway, including the CNG channel subunit A2 (CNGA2) (7), the G protein G olf (8), or adenylyl cyclase (AC) III (9), result in severe deficit of odorantevoked responses to many odorants, demonstrating the dominant role of the cAMP pathway.Semiochemicals, such as pheromones, social attractants, and major histocompatibility complex (MHC)-related odorants, signal social and sexual status, genetic makeup, and species identity important for the survival of the individual and the species (1, 10-13). Recent studies indicate that both the main olfactory epithelium (MOE) and olfactory bulbs respond to these chemosignals (14, 15). Consistent with these findings, sensory information from the main olfactory bulb projects to areas in the hypothalamus housing neurons that produce gonadotropinreleasing hormone and plays an important role in reproduction (16,17). Further, a class of chemosensory receptors that recognize social amines found in urine have been identified recently in the MOE (18). Thus, it now is clear that the main olfactory system is involved in detection of semiochemicals and that the cAMP signaling pathway plays an important role in signal transduction f...

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Pheromone Detection in Male Mice Depends on Signaling through the Type 3 Adenylyl Cyclase in the Main Olfactory Epithelium

Cited by 131 publications

References 29 publications

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

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

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

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