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See detailEffect of chronic intracerebroventricular administration of an aromatase inhibitor on the expression of social sexual behaviors in male Japanese quail.
Court, Lucas ULiege; Balthazart, Jacques ULiege; Ball, Gregory F et al

in Behavioural Brain Research (in press)

Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e ... [more ▼]

Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network. This network is directly implicated in the expression of a large range of social behaviors. The primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). An additional goal was to test the feasibility and effectiveness of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps using male sexual behavior as the aromatase dependent measure. We demonstrate that this mode of administration results in the strongest inhibition of both copulatory behavior and sexual motivation ever observed in this species, while other social behaviors were variably affected. Sexual motivation and the tendency to approach a group of conspecifics including females clearly seem to depend on brain aromatase, but the effects of central estrogen production on aggressive behavior and on the motivation to approach males remain less clear. [less ▲]

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See detailLONG TERM EFFECTS OF THE INHIBITION OF BRAIN AROMATASE ON THE EXPRESSION OF SOCIO-SEXUAL BEHAVIORS IN MALE JAPANESE QUAIL
Court, Lucas ULiege; Balthazart, Jacques ULiege; Ball, Gregory F et al

Conference (2021, February 26)

Aromatase converts androgens into estrogens in the brain of vertebrates including humans [2]. This enzyme is also expressed in other tissues [8] where its action may result in negative effects on human ... [more ▼]

Aromatase converts androgens into estrogens in the brain of vertebrates including humans [2]. This enzyme is also expressed in other tissues [8] where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors [3] but their central effects are poorly known in humans. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network [5,7]. This network is directly implicated in the expression of a large range of social behaviors. Given the potential implication of brain aromatase in a variety of behavioral processes, the primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase irrespective of its neuroanatomical location on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). The Japanese quail (Coturnix japonica) is an excellent experimental model to analyze the functions of brain aromatase since males of this species exhibit a dense expression of this enzyme in most nuclei of the social behavior network [4] and they display a large range of social behaviors in laboratory settings [1,6]. A secondary goal was to test the feasibility of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps. Adult male quail were implanted with a 200µl osmotic pump (Alzet®, Model 2004, 0.25µl per hour, 28 day expected duration) connected by a 25cm vinyl cannula tubing (C312VT; 0.69 x 1.14 mm; PlasticsOne®) to a single guide osmotic brain cannula (3220P/SPC, Cut 8 mm below pedestal; PlasticsOne®) implanted in the third ventricle. The osmotic pumps were loaded with either the aromatase inhibitor, vorozole™ (R76713 or VOR, Janssen Pharmaceutica, Beerse, Belgium; 50µg/µl in propylene glycol) or with the vehicle (propylene glycol) under sterile conditions. Birds were either sexually mature gonadally intact birds (Experiment 1) or had been castrated and treated with exogenous testosterone via a subcutaneous Silastic implant (Experiment 2). They were then tested over a period of about 3 weeks for a variety of social behavior including consummatory sexual behavior, appetitive sexual behavior assessed by the frequency of rhythmic cloacal sphincter movements (RCSM), aggressive behavior, sex partner preference, and social reinstatement motivation. These last two behaviors were measured in a 5-compartment corridor by quantifying the time spend near stimuli (male, female or groups of conspecifics) placed at the two ends. [less ▲]

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See detailEFFECT OF CHRONIC INTRACEREBROVENTRICULAR ADMINISTRATION OF AN AROMATASE INHIBITOR ON THE EXPRESSION OF SOCIO-SEXUAL BEHAVIORS IN MALE JAPANESE QUAIL
Court, Lucas ULiege; Balthazart, Jacques ULiege; Ball, Gregory F et al

Conference (2020, December 18)

Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e ... [more ▼]

Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network. This network is directly implicated in the expression of a large range of social behaviors. Given the potential implication of brain aromatase in a variety of behavioral processes, the primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). A secondary goal was to test the feasibility of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps. We demonstrate that this approach results in the strongest inhibition of both copulatory behavior and sexual motivation ever observed in this species, while other social behaviors were variably affected. Sexual motivation and the tendency to approach a group of conspecifics including females clearly seem to depend on brain aromatase, but the effects of central estrogen production on aggressive behavior and on the motivation to approach males remain less clear. [less ▲]

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See detailDevelopment of perineuronal nets during ontogeny correlates with sensorimotor vocal learning in canaries
Cornez, Gilles ULiege; Collignon, Clémentine ULiege; Müller, Went et al

in eNeuro (2020), 7(2), 0361-192020

Songbirds are a powerful model to study vocal learning given that aspects of the underlying behavioral and neurobiological mechanisms are analogous in many ways to mechanisms involved in speech learning ... [more ▼]

Songbirds are a powerful model to study vocal learning given that aspects of the underlying behavioral and neurobiological mechanisms are analogous in many ways to mechanisms involved in speech learning. Perineuronal nets (PNNs) represent one of the mechanisms controlling the closing of sensitive periods for vocal learning in the songbird brain. In zebra finches, PNN develop around parvalbumin (PV)-expressing interneurons in selected song control nuclei during ontogeny and their development is delayed if juveniles are deprived of a tutor. However, song learning in zebra finches takes place during a relatively short period of development, and it is difficult to determine whether PNN development correlates with the end of the sensory or the sensorimotor learning period. Canaries have a longer period of sensorimotor vocal learning, spanning over their first year of life so that it should be easier to test whether PNN development correlates with the end of sensory or sensorimotor vocal learning. Here, we quantified PNN around PV-interneurons in the brain of male canaries from hatching until the first breeding season and analyzed in parallel the development of their song. PNN development around PV-interneurons specifically took place and their number reached its maximum around the end of the sensorimotor learning stage, well after the end of sensory vocal learning, and correlated with song development. This suggests that PNN are specifically involved in the termination of the sensitive period for sensorimotor vocal learning. [less ▲]

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See detailKey role of estrogen receptor β in the organization of brain and behavior of the Japanese quail
Court, Lucas ULiege; Vandries, Laura ULiege; Balthazart, Jacques ULiege et al

in Hormones and Behavior (2020), 125

Estrogens play a key role in the sexual differentiation of the brain and behavior. While early estrogen actions exert masculinizing effects on the brain of male rodents, a diametrically opposite effect is ... [more ▼]

Estrogens play a key role in the sexual differentiation of the brain and behavior. While early estrogen actions exert masculinizing effects on the brain of male rodents, a diametrically opposite effect is observed in birds where estrogens demasculinize the brain of females. Yet, the two vertebrate classes express similar sex differences in the brain and behavior. Although ERα is thought to play a major role in these processes in rodents, the role of ERβ is still controversial. In birds, the identity of the estrogen receptor(s) underlying the demasculinization of the female brain remains unclear. The aim of the present study was thus to determine in Japanese quail the effects of specific agonists of ERα (propylpyrazole triol, PPT) and ERβ (diarylpropionitrile, DPN) administered at the beginning of the sensitive period (embryonic day 7, E7) on the sexual differentiation of male sexual behavior and on the density of vasotocin-immunoreactive (VT-ir) fibers, a known marker of the organizational action of estrogens on the quail brain. We demonstrate that estradiol benzoate and the ERβ agonist (DPN) demasculinize male sexual behavior and decrease the density of VT-ir fibers in the medial preoptic nucleus and the bed nucleus of the stria terminalis, while PPT has no effect on these measures. These results clearly indicate that ERβ, but not ERα, is involved in the estrogen-induced sexual differentiation of brain and sexual behavior in quail. © 2020 Elsevier Inc. [less ▲]

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See detailSeasonal changes of perineuronal nets and song learning in adult canaries (Serinus canaria)

Cornez, Gilles ULiege; Collignon, Clémentine ULiege; Müller, Went et al

in Behavioural Brain Research (2020), 380

Songbirds learn their song during a sensitive period of development associated with enhanced neural plasticity. In addition, in open-ended learners such as canaries, a sensitive period for sensorimotor ... [more ▼]

Songbirds learn their song during a sensitive period of development associated with enhanced neural plasticity. In addition, in open-ended learners such as canaries, a sensitive period for sensorimotor vocal learning reopens each year in the fall and leads to song modifications between successive breeding seasons. The variability observed in song production across seasons in adult canaries correlates with seasonal fluctuations of testosterone concentrations and with morphological changes in nuclei of the song control system (SCS). The sensitive periods for song learning during ontogeny and then again in adulthood could be controlled by the development of perineuronal nets (PNN) around parvalbumin-expressing interneurones (PV) which limits learning-induced neuroplasticity. However, this relationship has never been investigated in the context of adult vocal learning in adult songbirds. Here we explored PNN and PV expression in the SCS of adult male Fife Fancy canaries in relation to the seasonal variations of their singing behaviour. We found a clear pattern of seasonal variation in testosterone concentrations and song production. Furthermore, PNN expression was significantly higher in two specific song control nuclei, the robust nucleus of the arcopallium (RA) and the Area X of the basal ganglia, during the breeding season and during the later stages of sensorimotor song development compared to birds in an earlier stage of sensorimotor development during the fall. These data provide the first evidence that changes in PNN expression could represent a mechanism regulating the closing-reopening of sensitive periods for vocal learning across seasons in adult songbirds [less ▲]

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See detailSexually differentiated and neuroanatomically specific co-expression of aromatase neurons and GAD67 in the male and female quail brain
Cornil, Charlotte ULiege; Ball, Gregory F.; Balthazart, Jacques ULiege

in European Journal of Neuroscience (2020), 52(3), 2963-2981

Testosterone aromatization into estrogens in the preoptic area (POA) is critical for the activation of male sexual behavior in many vertebrates. Yet, cellular mechanisms mediating actions of ... [more ▼]

Testosterone aromatization into estrogens in the preoptic area (POA) is critical for the activation of male sexual behavior in many vertebrates. Yet, cellular mechanisms mediating actions of neuroestrogens on sexual behavior remain largely unknown. We investigated in male and female Japanese quail by dual-label fluorescent in situ hybridization (FISH) whether aromatase-positive (ARO) neurons express glutamic acid decarboxylase 67 (GAD67), the rate-limiting enzyme in GABA biosynthesis. AROcells and ARO cells double labeled with GAD67 (ARO-GAD67) were counted at standardized locations in the medial preoptic nucleus (POM) and the medial bed nucleus of the stria terminalis (BST) to produce three-dimensional distribution maps. Overall, males had more ARO cells than females in POM and BST. The numberof double-labeled ARO-GAD67 cells was also higher in males than in females and greatly varied as a function of the specific position in these nuclei. Significant sex differences were however present only in the most caudal part of POM.Although both ARO and GAD67 were expressed in the VMN, no colocalization between these markers was detected.Together, these data show that a high proportion of estrogen synthesizing neurons in POM and BST are inhibitory and the colocalization of GAD67 with AROexhibits a high degree of anatomical specificity as well as localized sex differences. The fact that many preoptic ARO neurons project to the periaqueductal gray in male quail suggests possible mechanisms through which locally produced estrogens could activate male sexual behavior. [less ▲]

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See detailHow technical progress reshaped behavioral neuroendocrinology during the last 50 years… and some methodological remarks
Balthazart, Jacques ULiege

in Hormones and Behavior (2020), 118

The first issue of Hormones and Behavior was published 50 years ago in 1969, a time when most of the techniques we currently use in Behavioral Endocrinology were not available. Researchers have during the ... [more ▼]

The first issue of Hormones and Behavior was published 50 years ago in 1969, a time when most of the techniques we currently use in Behavioral Endocrinology were not available. Researchers have during the last 5 decades developed techniques that allow measuring hormones in small volumes of biological samples, identify the sites where steroids act in the brain to activate sexual behavior, characterize and quantify gene expression correlated with behavior expression, modify this expression in a specific manner, and manipulate the activity of selected neuronal populations by chemogenetic and optogenetic techniques. This technical progress has considerably transformed the field and has been very beneficial for our understanding of the endocrine controls of behavior in general, but it did also come with some caveats. The facilitation of scientific investigations came with some relaxation of methodological exigency. Some critical controls are no longer performed on a regular basis and complex techniques supplied as ready to use kits are implemented without precise knowledge of their limitations. We present here a selective review of the most important of these new techniques, their potential problems and how they changed our view of the hormonal control of behavior. Fortunately, the scientific endeavor is a self-correcting process. The problems have been identified and corrections have been proposed. The next decades will obviously be filled with exciting discoveries in behavioral neuroendocrinology. © 2020 Elsevier Inc. [less ▲]

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See detailIn vivo online monitoring of testosterone-induced neuroplasticity in a female songbird
Orije, J.; Cardon, E.; De Groof, G. et al

in Hormones and Behavior (2020), 118

Adult neuroplasticity in the song control system of seasonal songbirds is largely driven by photoperiod-induced increases in testosterone. Prior studies of the relationships between testosterone, song ... [more ▼]

Adult neuroplasticity in the song control system of seasonal songbirds is largely driven by photoperiod-induced increases in testosterone. Prior studies of the relationships between testosterone, song performance and neuroplasticity used invasive techniques, which prevent analyzing the dynamic changes over time and often focus on pre-defined regions-of-interest instead of examining the entire brain. Here, we combined (i) in vivo diffusion tensor imaging (DTI) to assess structural neuroplasticity with (ii) repeated monitoring of song and (iii) measures of plasma testosterone concentrations in thirteen female photosensitive starlings (Sturnus vulgaris) who received a testosterone implant for 3 weeks. We observed fast (days) and slower (weeks) effects of testosterone on song behavior and structural neuroplasticity and determined how these effects correlate on a within-subject level, which suggested separate contributions of the song motor and anterior forebrain pathways in the development of song performance. Specifically, the increase in testosterone correlated with a rapid increase of song rate and RA volume, and with changes in Area X microstructure. After implant removal, these variables rapidly reverted to baseline levels. In contrast, the more gradual improvement of song quality was positively correlated with the fractional anisotropy values (DTI metric sensitive to white matter changes) of the HVC-RA tract and of the lamina mesopallialis, which contains fibers connecting the song control nuclei. Thus, we confirmed many of the previously reported testosterone-induced effects, like the increase in song control nuclei volume, but identified for the first time a more global picture of the spatio-temporal changes in brain plasticity. © 2019 Elsevier Inc. [less ▲]

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See detailMolecular correlates of hypothalamic development in songbird ontogeny in comparison with the telencephalon
Majumdar, G.; Yadav, G.; Hamaide, J. et al

in FASEB Journal (2020)

Development of the songbird brain provides an excellent experimental model for understanding the regulation of sex differences in ontogeny. Considering the regulatory role of the hypothalamus in endocrine ... [more ▼]

Development of the songbird brain provides an excellent experimental model for understanding the regulation of sex differences in ontogeny. Considering the regulatory role of the hypothalamus in endocrine, in particular reproductive, physiology, we measured the structural (volume) and molecular correlates of hypothalamic development during ontogeny of male and female zebra finches. We quantified by relative quantitative polymerase chain reaction (rqPCR) the expression of 14 genes related to thyroid and steroid hormones actions as well as 12 genes related to brain plasticity at four specific time points during ontogeny and compared these expression patterns with the expression of the same genes as detected by transcriptomics in the telencephalon. These two different methodological approaches detected specific changes with age and demonstrated that in a substantial number of cases changes observed in both brain regions are nearly identical. Other genes however had a tissue-specific developmental pattern. Sex differences or interactions of sex by age were detected in the expression of a subset of genes, more in hypothalamus than telencephalon. These results correlate with multiple known aspects of the developmental and reproductive physiology but also raise a number of new functional questions. © 2020 Federation of American Societies for Experimental Biology [less ▲]

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See detailTestosterone stimulates perineuronal nets development around parvalbumin cells in the adult canary brain in parallel with song crystallization.
Cornez, Gilles ULiege; Schevchouk, Olesya; Ghorbanpoor, Samar et al

in Hormones and Behavior (2020), 119

Perineuronal nets (PNN) of the extracellular matrix are dense aggregations of chondroitin-sulfate proteoglycans that usually surround fast-spiking parvalbumin-expressing inhibitory interneurons (PV). The ... [more ▼]

Perineuronal nets (PNN) of the extracellular matrix are dense aggregations of chondroitin-sulfate proteoglycans that usually surround fast-spiking parvalbumin-expressing inhibitory interneurons (PV). The development of PNN around PV appears specifically at the end of sensitive periods of visual learning and limits the synaptic plasticity in the visual cortex of mammals. Seasonal songbirds display a high level of adult neuroplasticity associated with vocal learning, which is regulated by fluctuations of circulating testosterone concentrations. Seasonal changes in testosterone concentrations and in neuroplasticity are associated with vocal changes between the non-breeding and breeding seasons. Increases in blood testosterone concentrations in the spring lead to the annual crystallization of song so that song becomes more stereotyped. Here we explore whether testosterone also regulates PNN expression in the song control system of male and female canaries. We show that, in both males and females, testosterone increases the number of PNN and of PV neurons in the three main telencephalic song control nuclei HVC, RA (nucleus robustus arcopallialis) and Area X and increases the PNN localization around PV interneurons. Singing activity was recorded in males and quantitative analyses demonstrated that testosterone also increased male singing rate, song duration and song energy while decreasing song entropy. Together, these data suggest that the development of PNN could provide the synaptic stability required to maintain the stability of the testosterone-induced crystallized song. This provides the new evidence for a role of PNN in the regulation of adult seasonal plasticity in seasonal songbirds [less ▲]

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See detailComparing perineuronal nets and parvalbumin development between black bird species with differences in early developmental song exposure
Cornez, Gilles ULiege; Langro, Justin; Cornil, Charlotte ULiege et al

in Journal of Experimental Biology (2020), 223(Pt1), 212910

Brood parasitic songbirds are a natural system in which developing birds are isolated from species-typical song and therefore present a unique opportunity to compare neural plasticity in song learners ... [more ▼]

Brood parasitic songbirds are a natural system in which developing birds are isolated from species-typical song and therefore present a unique opportunity to compare neural plasticity in song learners raised with and without conspecific tutors. We compared perineuronal nets (PNN) and parvalbumin (PV) in song control nuclei in juveniles and adults of two closely related icterid species (i.e. blackbirds): brown-headed cowbirds (Molothrus ater; brood parasite) and red-winged blackbirds (Agelaius phoeniceus; non-parasite). The number of PV cells per nucleus was significantly higher in adults compared with juveniles in the nucleus HVC and the robust nucleus of the arcopallium (RA), whereas no significant species difference appeared in any region of interest. The number of PNN per nuclei was significantly higher in adults compared with juveniles in HVC, RA and Area X, but only RA exhibited a significant difference between species. PV cells surrounded by PNN (PV+PNN) also exhibited age-related differences in HVC, RA and Area X, but RA was the only region in which PV+PNN exhibited significant species differences. Furthermore, a significant interaction existed in RA between age and species with respect to PNN and PV+PNN, revealing RA as a region displaying differing plasticity patterns across age and species. Additional comparisons of PNN and PV between adult male and female cowbirds revealed that males have greater numbers of all three measures in RA compared with females. Species-, sex- and age-related differences in RA suggest that species differences in neural plasticity are related to differences in song production rather than sensitivity to song learning, despite a stark contrast in early exposure to conspecific male tutors. [less ▲]

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See detailL’expérimentation animale : toujours une nécessité pour la santé animale et humaine
Balthazart, Jacques ULiege; Blanpain, Cédric; Bureau, Fabrice ULiege et al

Article for general public (2019)

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l ... [more ▼]

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l'une des premières causes de décès en Belgique. Cet article soulignait l'importance de la recherche fondamentales et du passage nécessaire par l'expérimentation préclinique (animale) pour développer une application chez l’humain. En réaction, Solange T'Kint, administratrice de l'ASBL S.E.A. - Suppression des Expériences sur l'Animal-, publiait le 2 juillet dans « La Libre » un nouveau pamphlet contre l'expérimentation animale. Mme T Kint avait déjà lancé en aout 2018 une pétition attaquant la découverte3 d'un chercheur de l'ULB sur la dépendance aux drogues réalisée chez la souris , démontrant par là à quel point toute avancée médicale imputable à l'expérimentation animale lui est insupportable. Ici se trouve la réponse de Scientifiques qui pensent indispensable d’informer chacun-e- de manière rigoureuse et de ne jamais laisser diffuser de « fake news » sans réagir. [less ▲]

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See detailMale sexual behavior and hormones in non-mammalian vertebrates
Balthazart, Jacques ULiege; Ball, G. F.

in Encyclopedia of Animal Behavior (2019)

In most vertebrate species, male sexual behavior is activated by the action of testosterone on the preoptic area and in many cases this behavioral activation requires transformation of the steroid into ... [more ▼]

In most vertebrate species, male sexual behavior is activated by the action of testosterone on the preoptic area and in many cases this behavioral activation requires transformation of the steroid into estradiol and 5a-dihydrotestosterone. These metabolites, either alone or in synergy, act at the cellular level to produce changes in neuronal function that mediate behavioral changes. Variation in plasma testosterone concentrations does not simply correlate in a positive manner with the degree of behavioral activation. For example, in many species, testosterone cannot activate male-typical sexual behaviors in females. This sex difference in the behavioral consequences of testosterone results from organizational effects of sex steroids that irreversibly differentiate the brain during ontogeny so that male brains will respond in adulthood to testosterone while female brains will not. Behavioral effects of testosterone are largely mediated by changes in the transcription of specific proteins, including enzymes that synthesize or catabolize neurotransmitters and their receptors. These changes in protein expression in turn produce changes in neurotransmission in a defined neuronal circuitry that supports behavior expression. There are more recently described effects of steroids that do not involve protein transcription but rather involve actions at the neuronal membrane or direct changes in intracellular signaling cascades that also seem to contribute to the control of male sexual behavior. These principles seem to apply to a wide range of non-mammalian vertebrate species though a number of specialized reproductive strategies that could be associated with exceptions to these general rules have also been described. [less ▲]

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See detailNew concepts in the study of the sexual differentiation and activation of reproductive behavior, a personal view
Balthazart, Jacques ULiege

in Frontiers in Neuroendocrinology (2019), 55

Since the beginning of this century, research methods in neuroendocrinology enjoyed extensive refinements and innovation. These advances allowed collection of huge amounts of new data and the development ... [more ▼]

Since the beginning of this century, research methods in neuroendocrinology enjoyed extensive refinements and innovation. These advances allowed collection of huge amounts of new data and the development of new ideas but have not led to this point, with a few exceptions, to the development of new conceptual advances. Conceptual advances that took place largely resulted from the ingenious insights of several investigators. I summarize here some of these new ideas as they relate to the sexual differentiation and activation by sex steroids of reproductive behaviors and I discuss how our research contributed to the general picture. This selective review clearly demonstrates the importance of conceptual changes that have taken place in this field since beginning of the 21st century. The recent technological advances suggest that our understanding of hormones, brain and behavior relationships will continue to improve in a very fundamental manner over the coming years. © 2019 Elsevier Inc. [less ▲]

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See detailHow does testosterone act to regulate a multifaceted adaptive response? Lessons from studies of the avian song system
Ball, G. F.; Madison, F. N.; Balthazart, Jacques ULiege et al

in Journal of Neuroendocrinology (2019)

In male songbirds, song functions to attract a mate or to defend a territory; it is therefore often produced in the context of reproduction. Testosterone of gonadal origin increases during the ... [more ▼]

In male songbirds, song functions to attract a mate or to defend a territory; it is therefore often produced in the context of reproduction. Testosterone of gonadal origin increases during the reproductive phase of the annual cycle and significantly enhances song production, as well as song development, via effects on song crystallisation. The neural control of birdsong production and learning is highly modular. We implanted testosterone or androgen antagonists into specific brain regions or in the periphery of castrated male canaries and, in this way, identified how androgen signalling in specific locations regulates a variety of birdsong features. For example, castrated male canaries treated with testosterone in the preoptic area only and exposed to long days sing at high rates compared to castrated male canaries not treated with testosterone. However, these birds with testosterone in the preoptic area still produce songs with substantially lower song stereotypy and amplitude; these features are controlled by testosterone acting in the song control nuclei HVC and robust nucleus of the arcopallium. Specific aspects of the learned singing behaviour are thus regulated by androgens acting at multiple levels in the brain in a non-redundant fashion. The action of testosterone in the preoptic area is related to the hormonal regulation of the motivation to sing but not to various aspects of song performance. Multiple aspects of song quality are instead precisely regulated by steroids acting in distinct song control nuclei. Females exert a strong choice for specific features of male song in canaries and this choice is influenced by the endocrine state of the female. The female song system is also involved in song production, as well as song perception, although the specificity of this hormone action has not yet been investigated. © 2019 British Society for Neuroendocrinology [less ▲]

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See detailThe neuroendocrine integration of environmental information, the regulation and action of testosterone and the challenge hypothesis
Ball, G. F.; Balthazart, Jacques ULiege

in Hormones and Behavior (2019)

The authors of the original challenge hypothesis proposed influential hypotheses concerning the relationship between testosterone concentrations in the blood and aggressive social behaviors. Many of the ... [more ▼]

The authors of the original challenge hypothesis proposed influential hypotheses concerning the relationship between testosterone concentrations in the blood and aggressive social behaviors. Many of the key observations were made in avian species studied in the wild and in captivity. In this review we evaluate some remaining questions about the ideas discussed in the challenge hypothesis from a neuroendocrine perspective. For example, a rise in testosterone in response to a social aggressive stimulus might involve complex social information being processed by the brain and an appropriate signal sent to the gonadotrophin-releasing hormone (GnRH) neuronal system. Alternatively, social stimuli could more directly stimulate the testis and testosterone release via sympathetic innervation of the testis though such pathways have not been linked to a response to social behaviors. The social behavior decision network in the brain seems to play a key role in the regulation of aggressive behavior but how sensory information concerning aggressive behaviors is interpreted appropriately, processed by the social decision network and sent to the GnRH system is still not well understood. There are continuing questions about the extensive species variation in whether an increase in testosterone occurs in response to a territorial challenge, what its function might be and whether increases in testosterone are necessary to activate morphological changes, or the expression of sexual and aggressive behaviors associated with successful reproduction. © 2019 [less ▲]

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See detailEffects of a novel partner and sexual satiety on the expression of male sexual behavior and brain aromatase activity in quail.
de Bournonville, Catherine ULiege; Schmit, Mélanie; Telle, Maxime et al

in Behavioural Brain Research (2019), 359

This study was designed to determine whether changes in sexual motivation acutely regulate brain estrogen synthesis by aromatase. Five experiments (Exp.1–5) were first conducted to determine the effect of ... [more ▼]

This study was designed to determine whether changes in sexual motivation acutely regulate brain estrogen synthesis by aromatase. Five experiments (Exp.1–5) were first conducted to determine the effect of recent mating and of the presentation of a new female (Coolidge effect) on sexual motivation. Exp.1–2 showed that 10 min or overnight access to copulation decreases measures of male sexual motivation when male subjects were visually exposed to the female they had copulated with and this effect is not counteracted by the view of a new female. Exp.3 showed that sexual motivation is revived by the view of a new female in previously unmated males only allowed to see another female for 10 min. After mating for 10 min (Exp.4) or overnight (Exp.5) with a female, males showed a decrease in copulatory behavior that was not reversed by access to a new female. Exp.6 and 7 confirmed that overnight copulation (Exp.6) and view of a novel female (Exp.7) respectively decreases and increases sexual behavior and motivation. Yet, these manipulations did not affect brain aromatase activity except in the tuberal hypothalamus. Together these data confirm that copulation or prolonged view of a female de- crease sexual motivation but a reactivation of sexual motivation by a new female can only be obtained if males had only seen another female but not copulated with her, which is different in some degree from the Coolidge effect described in rodents. Moreover changes in brain aromatase do not simply reflect changes in motivation and more complex mechanisms must be considered. [less ▲]

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See detailSite-specific effects of aromatase inhibition on the activation of male sexual behavior in male Japanese quail (Coturnix japonica)
de Bournonville, Marie-Pierre ULiege; Vandries, Laura ULiege; Ball, Gregory et al

in Hormones and Behavior (2019), 108

Aromatization within the medial preoptic nucleus (POM) is essential for the expression of male copulatory behavior in Japanese quail. However, several nuclei within the social behavior network (SBN) also ... [more ▼]

Aromatization within the medial preoptic nucleus (POM) is essential for the expression of male copulatory behavior in Japanese quail. However, several nuclei within the social behavior network (SBN) also express aromatase. Whether aromatase in these loci participates in the behavioral activation is not known. Castrated male Japanese quail were implanted with 2 subcutaneous Silastic capsules filled with crystalline testosterone and with bilateral stereotaxic implants filled with the aromatase inhibitor Vorozole targeting the POM, the bed nucleus of the stria terminalis (BST) or the ventromedial nucleus of the hypothalamus (VMN). Control animals were implanted with testosterone and empty bilateral stereotaxic implants. Starting 2 days after the surgery, subjects were tested for the expression of consummatory sexual behavior (CSB) every other day for a total of 10 tests. They were also tested once for appetitive sexual behavior (ASB) as measured by the rhythmic cloacal sphincter movements displayed in response to the visual presentation of a female. CSB was drastically reduced when the Vorozole implants were localized in the POM, but not in the BST nor in the VMN. Birds with implants in the BST showed a longer latency to show CSB in the first 6 tests than controls, suggesting a role of the BST in the acquisition of the full copulatory ability. ASB was not significantly affected by aromatase blockade in any region. These data confirm the key role played by the POM in the control of male sexual behavior and suggest a minor role for aromatization in the BST or VMN. [less ▲]

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See detailTestosterone or estradiol when implanted in the medial preoptic nucleus trigger short low-amplitude songs in female canaries
Vandries, Laura ULiege; Ghorbanpoor, Samar; Cornez, Gilles ULiege et al

in eNeuro (2019), 6(2), 0502-182019

In male songbirds, the motivation to sing is largely regulated by testosterone action in the medial preoptic area, whereas testosterone acts on song control nuclei to modulate aspects of song quality ... [more ▼]

In male songbirds, the motivation to sing is largely regulated by testosterone action in the medial preoptic area, whereas testosterone acts on song control nuclei to modulate aspects of song quality. Stereotaxic implantation of testosterone in the medial preoptic nucleus (POM) of castrated male canaries activates a high rate of singing activity, albeit with a longer latency than after systemic testosterone treatment. Systemic testosterone also increases the occurrence of male-like song in female canaries. We hypothesized that this effect is also mediated by testosterone action in the POM. Females were stereotaxically implanted with either testosterone or with estradiol targeted at the POM and their singing activity was recorded daily during 2 hours for 28 days until brains were collected for histological analyses. Following identification of implant localizations, 3 groups of subjects were constituted that had either testosterone or estradiol implanted in the POM or had an implant that had missed the POM (Out). Testosterone and estradiol in POM significantly increased the number of songs produced and the percentage of time spent singing as compared with the Out group. The songs produced were in general of a short duration and of poor quality. This effect was not associated with an increase in HVC volume as observed in males, but testosterone in POM enhanced neurogenesis in HVC, as reflected by an increased density of doublecortin-immunoreactive multipolar neurons. These data indicate that, in female canaries, testosterone acting in the POM plays a significant role in hormone-induced increases in the motivation to sing. [less ▲]

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