Matthieu Keller

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

In the field of sensory perception, one noticeable fact regarding olfactory perception is the existence of several olfactory subsystems involved in the detection and processing of olfactory information. Indeed, the vomeronasal or accessory olfactory system is usually conceived as being involved in the processing of pheromones as it is closely connected to the hypothalamus, thereby controlling reproductive function. By contrast, the main olfactory system is considered as a general analyzer of volatile chemosignals, used in the context of social communication, for the identification of the status of conspecifics. The respective roles played by the main and the accessory olfactory systems in the control of mate recognition and sexual behavior are at present still controversial. We summarize in this review recent results showing that both the main and accessory olfactory systems are able to process partially overlapping sets of sexual chemosignals and that both systems support complimentary aspects in mate recognition and in the control of sexual behavior.

Olfactory mediation of maternal behavior in selected mammalian species

The aim of this review is to show how olfaction is a sensory modality of singular importance for the fine adjustment of early mother-infant interactions. While the precise role of maternal olfaction varies from one species to another, olfactory cues are in fact used in various aspects of parental care. Not only do infantile odors become very potent stimuli allowing the normal development of maternal care but they also provide a basis for individual recognition of the offspring in some species. Recognizable olfactory signatures reflected the product of individuals genotype and are also influenced by the environment. Highly specialized neural mechanisms for processing of the infant signals have been developed. While there is no functional specificity of either the main or the accessory olfactory systems in the onset of maternal behavior among species, only the main olfactory system is implicated when individual odor discrimination of the young is required. Neural structures, such as the main olfactory bulb, undergo profound changes when exposed to offspring odors at parturition. These changes in synaptic circuitry contribute both to maternal responsiveness to these odors and to their memorization.

Mapping of Kisspeptin Fibres in the Brain of the Pro-Oestrous Rat

Kisspeptins are a family of small peptides that play a key role in the neuroendocrine regulation of the reproductive function through neural pathways that have not yet been completely identified. The present study aimed to investigate the distribution of kisspeptin neurone fibres in the female rat brain by comparing precisely the immunoreactive pattern obtained with two antibodies: one specifically directed against kisspeptin‐52 (Kp‐52), the longest isoform, and the other directed against kisspeptin‐10 (Kp‐10), whose sequence is common to all putative mature isoforms. With both antibodies, immunoreactive cell bodies were exclusively observed in the arcuate nucleus, and immunoreactive fibres were confined to the septo‐preoptico‐hypothalamic continuum of the brain. Fibres were observed in the preoptic area, the diagonal band of Broca, the septohypothalamic area, the anteroventral periventricular, suprachiasmatic, supraoptic, paraventricular and periventricular nuclei, the dorsal border of the ventromedian nucleus, the dorsomedial and arcuate nuclei, and the median eminence. In the latter structure, varicose fibres were mainly distributed in the internal layer and were detected to a lesser extent throughout the external layer, including around the deeper part of the infundibular recess. Most regions of immunoreactive cells and fibres matched perfectly for the two antibodies. However, fibres in the dorsolateral septum, anterior fornix, accumbens nucleus and the lateral bed nucleus of the stria terminalis were only recognised by antibody anti‐Kp‐10, suggesting that anti‐Kp‐10 may recognise a wider range of kisspeptin isoforms than anti‐Kp‐52 or cross‐react with molecules other than kisspeptin in rat tissue. Overall, these results illustrate the variety of projection sites of kisspeptin neurones in the rat and suggest that these peptides play a role in different functions.

Mother-young relationships in sheep: a model for a multidisciplinary approach of the study of attachment in mammals.

The onset of maternal responsiveness and the development of mother–young attachment in sheep are under the combined influence of hormonal and sensory stimulations. In the mother, the prepartum rise in oestrogen and vaginocervical stimulation caused by expulsion of the foetus act on the main olfactory system and on hypothalamic regions. This induces maternal care through the central release of oxytocin, modulated by opiates and corticotrophin‐releasing hormone. In parallel, activation of the main olfactory network enables the learning of individual lamb odour and maternal attachment. In the neonate, the first suckling episodes and the concomitant activation of the cholecystokinin, opioids and oxytocin systems facilitate the development of a preference for the mother. Gastrointestinal signals activate the brain stem, the hypothalamus and the amygdala. Within 72 h of parturition, the mother–young attachment shifts from proximal to distal recognition based on visual and auditory cues after which vocal cues become more salient. Although olfaction remains a key element in the display of selective maternal nursing, maternal attachment relies on a multisensory mental image of the lamb. These findings support the view that sheep are amongst the most appropriate animal models for the study of maternal and filial attachment in mammals.

Cortical and medial amygdala are both involved in the formation of olfactory offspring memory in sheep

Ewes form a selective olfactory memory for their lambs after 2 h of mother–young interaction following parturition. Once this recognition is established, ewes will subsequently reject any strange lamb approaching the udder (i.e. maternal selectivity). The present study tested the functional contribution of different amygdala nuclei to lamb olfactory memory formation. Using the anaesthetic lidocaine, cortical, medial or basolateral nuclei of the amygdala were transiently inactivated during lamb odour memory formation. Reversible inactivation of either cortical or medial amygdala during the first 8 h postpartum impaired lamb olfactory recognition, whereas inactivation of the basolateral nucleus or infusion of artificial cerebrospinal fluid did not. Control experiments indicate that inactivation of the cortical and medial nuclei of the amygdala specifically disrupt memory formation rather than olfactory perception or memory retrieval. These findings show that both nuclei of the amygdala are required for the formation of a lamb olfactory memory and suggest functional interaction between these two nuclei.

Short Term Treatment with Estradiol Decreases the Rate of Newly Generated Cells in the Subventricular Zone and Main Olfactory Bulb of Adult Female Mice

Adult neurogenesis occurs most notably in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the olfactory bulb (OB) where new neurons are generated from neural progenitors cells produced in the subventricular zone (SVZ) of the forebrain. As it is well known that gonadal steroid hormones, primarily estradiol, modulate neurogenesis in the hippocampus of adult female rodents, we wanted to determine whether estradiol would also affect the proliferation of progenitor cells in the SVZ and by consequence the rate of newly generated cells in the main OB. Thus a first group of adult female C57Bl6/J mice was ovariectomized and received a short term treatment with estradiol (single injection of 1 or 10 microg 17beta-estradiol or Silastic capsule of estradiol during 2 days) before receiving a single injection with BrdU to determine whether estradiol would modulate the cell proliferation in the SVZ. A second group of adult ovariectomized female mice was submitted to the same estradiol treatment before receiving four BrdU injections, and was sacrificed 21 days later to determine whether a modulation in cell proliferation actually leads to a modulation in the number of newborn cells in the main OB. We observed a decrease in cell proliferation in the SVZ following either dose of estradiol compared to the controls. Furthermore, 21 days after their generation in the SVZ, the number of BrdU labeled cells was also lower in the main OB, both in the granular and periglomerular cell layers of estradiol-treated animals. These results show that a short term treatment with estradiol actually downregulates cell proliferation leading to a decreased number of newborn cells in the OB.

Mapping of brain networks involved in consolidation of lamb recognition memory.

In sheep, ewes at parturition are responsive to any newborn lamb, but within less than 1 h, mothers learn to recognize the odor of their lamb and restrict maternal care to their own offspring (maternal selectivity). In a first experiment, we investigated the long-term retention of maternal selectivity after various mother-young contact and separation durations. After 4 h of contact, 36 h of separation leads to a total loss of selectivity. Increasing contact duration to 7 days prior to this separation maintains selectivity. These data suggest that lamb memory after going through an initial labile state after parturition, is consolidated over time into a more stable long-term memory. Fos immunohistochemistry reveals that reintroduction of the lamb after 4 h of mother-young contact and 3 h of separation activates different maternal brain regions than reintroduction of the lamb after 7 days of mother-young contact and 3 h of separation. While the piriform cortex shows an enhanced activation at both times, a selective enhancement of activation is observed in the frontal medial and orbitofrontal cortices only after 7 days of mother-young contact. These data suggest that as consolidation occurs, the neurobiological networks sustaining lamb memory involve different structures.

Perinatal visceral events and brain mechanisms involved in the development of mother-young bonding in sheep.

In sheep the onset of maternal responsiveness and the development of the mutual mother-young bond are under the combined influence of hormonal and visceral somatosensory stimulations. These stimuli are provided in the mother by parturition (via steroids and vaginocervical stimulation) and in the neonate by the first suckling episodes (via cholecystokinin and oro-gastro-intestinal stimulation). In addition, each partner relies on specific chemosensory stimulation for reciprocal attraction: amniotic fluids for the mother, colostrum for the young. In the ewe parturition activates several brain structures to respond specifically to sensory cues emanating from the young. The main olfactory bulbs undergo profound neurophysiological changes when exposed to offspring odors at parturition. Additional activations in the hypothalamus - preoptic area - and the amygdala - medial and cortical nuclei - also contribute to maternal responsiveness and memorization of lamb odors. In the neonate, post-ingestive stimulations activate the brain stem via vagal afferents. Like in the ewe, several regions of the hypothalamus and the amygdala respond to colostrum ingestion suggesting common ground for the integrative neural processes involved in early learning and bonding. This leads to rapid visual and auditory recognition in both partners although olfaction remains important in the ewe to display selective nursing. It is concluded that the biological basis for the development of maternal and filial bonding in sheep presents striking similarities.

A wide range of pheromone-stimulated sexual and reproductive behaviors in female mice depend on G protein Gαo.

BackgroundOptimal reproductive fitness is essential for the biological success and survival of species. The vomeronasal organ is strongly implicated in the display of sexual and reproductive behaviors in female mice, yet the roles that apical and basal vomeronasal neuron populations play in controlling these gender-specific behaviors remain largely unclear.ResultsTo dissect the neural pathways underlying these functions, we genetically inactivated the basal vomeronasal organ layer using conditional, cell-specific ablation of the G protein Gαo. Female mice mutant for Gαo show severe alterations in sexual and reproductive behaviors, timing of puberty onset, and estrous cycle. These mutant mice are insensitive to reproductive facilitation stimulated by male pheromones that accelerate puberty and induce ovulation. Gαo-mutant females exhibit a striking reduction in sexual receptivity or lordosis behavior to males, but gender discrimination seems to be intact. These mice also show a loss in male scent preference, which requires a learned association for volatile olfactory signals with other nonvolatile ownership signals that are contained in the high molecular weight fraction of male urine. Thus, Gαo impacts on both instinctive and learned social responses to pheromones.ConclusionsThese results highlight that sensory neurons of the Gαo-expressing vomeronasal subsystem, together with the receptors they express and the molecular cues they detect, control a wide range of fundamental mating and reproductive behaviors in female mice.

Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice

Bisphenol A (BPA) is a widespread estrogenic compound. We investigated the effects of maternal exposure to BPA at reference doses on sexual behavior and neuroendocrine functions of female offspring in C57BL/6J mice. The dams were orally exposed to vehicle alone or vehicle-containing BPA at doses equivalent to the no observed adverse effect level (5 mg/kg body weight per day) and tolerable daily intake (TDI, 0.05 mg/kg body weight per day) level from gestational day 15 until weaning. Developmental exposure to BPA increased the lordosis quotient in naive females exposed to BPA at the TDI dose only. BPA exposure had no effect on olfactory preference, ability to express masculine behaviors or number of calbindin-positive cells, a sexually dimorphic population of the preoptic area. BPA at both doses selectively increased kisspeptin cell number in the preoptic periventricular nucleus of the rostral periventricular area of the third ventricle in adult females. It did not affect the number of GNRH-positive cells or percentage of kisspeptin appositions on GNRH neurons in the preoptic area. These changes were associated with higher levels of estradiol (E2) at the TDI dose while levels of LH, estrus cyclicity, ovarian and uterine weights, and fertility remained unaffected. Delay in the time of vaginal opening was observed during the postnatal period at TDI dose, without any alteration in body growth. This shows that developmental exposure to BPA at reference doses did not masculinize and defeminize the neural circuitry underlying sexual behavior in female mice. The TDI dose specifically exacerbated responses normally induced by ovarian E2, through estrogen receptor α, during the postnatal/prepubertal period.