Publications of Charlotte Cornil
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See detailPhotoperiodic control of singing behavior and reproductive physiology in male fife fancy canaries
Chiver, Ioana ULiege; LALLEMAND, François ULiege; Cornil, Charlotte ULiege et al

Poster (2021, June 29)

Temperate-zone birds often display marked seasonal changes in reproductive behaviors and in the underlying hormonal and neural mechanisms. These changes have been extensively studied in canaries (Serinus ... [more ▼]

Temperate-zone birds often display marked seasonal changes in reproductive behaviors and in the underlying hormonal and neural mechanisms. These changes have been extensively studied in canaries (Serinus canaria) and there is emerging evidence of variation among strains in physiological responses to seasonal cues. Fife fancy male canaries were previously shown to change their reproductive physiology in response to variations in day length but it remained unclear whether they display absolute refractoriness, as Border canaries do, or only display relative refractoriness or simply track day length to control gonadal activity, singing behavior and the associated neural plasticity. Male birds maintained on 8L:16D (SD) for 6 months that had become reproductively competent (high song output and large testes) were divided into two groups: control birds remained on SD and experimental birds were switched to long days (16L:8D). During the following 11 weeks, singing behavior (recorded and quantitatively analyzed for 3X2 hours everyweek) and gonadal size (repeatedly measured by CT X-ray scans) remained similar for birds in both groups except for trill numbers that increased in the experimental group. Prolonged exposure to SD had thus induced a nearly full activation of reproductive physiology and behavior. Day length was then decreased back to 8L:16D for experimental birds which immediately induced a cessation of song, a decrease in testes size and a decrease in the volume of song control nuclei (Area X, HVC, RA). These data demonstrate that Fife fancy canaries sharply respond to changes in photoperiod but only display relative photorefractoriness. [less ▲]

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See detailFurther investigation of the rapid control of male sexual behavior by neuroestrogens in mice
de Bournonville, Catherine ULiege; Lemoine, Philippine ULiege; Foidart, Jean-Michel ULiege et al

Poster (2021, June 29)

Neuroestrogens play a key role in the activation of male sexual behavior by testosterone through their nuclear- and membrane-initiated actions. Studies conducted in birds suggested that membrane vs ... [more ▼]

Neuroestrogens play a key role in the activation of male sexual behavior by testosterone through their nuclear- and membrane-initiated actions. Studies conducted in birds suggested that membrane vs. nuclear actions of neuroestrogens differentially control sexual motivation and performance. In mice, estrogen receptor alpha (ERα) plays a major role in the control of male sexual behavior. However, whether the translocation ERα and its activation at the membrane rapidly affect male sexual behavior remains unclear. Recently, a mouse model (C451A-ERα) carrying a mutated ERα unable to traffic to and signal from the membrane was generated. Moreover, the natural estrogen estetrol (E4) has been described to act as an agonist of nuclear estrogen receptors but as an antagonist on their membrane-associated fraction. Here, we used the complementary properties of estetrol and C451A-ERα mice to investigate the role of membrane ERα (mERα) on male sexual motivation and performance. Regardless of the genotype, systemic aromatase blockade decreased within 10 min sexual performance and motivation, measured by the time spent close to an estrous female. E4 rapidly decreased sexual performance only in wild-type males and had no effect on sexual motivation. Together, these data confirmed the key role of aromatization in the rapid control of male sexual performance and extended this conclusion to sexual motivation. Moreover, E4, likely acting on mERα rapidly inhibits sexual performance, but not sexual motivation. Finally, the inhibitory effect of aromatase blockade in C451A-ERα mice suggests that another estrogen receptor than mERα also regulates both aspects of male sexual behavior. [less ▲]

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See detailActivational effects of androgens and estrogens can not reverse sex differences in song behavior and the song control nuclei in adult male and female canaries
Barros Dos Santos, Ednei ULiege; Ball, Gregory F; Cornil, Charlotte ULiege et al

Poster (2021, May 29)

Treatments with testosterone (T) do not activate singing behavior nor promote growth of song control nuclei to the same extend in male and female canaries (Serinus canaria). Because T acts in part via ... [more ▼]

Treatments with testosterone (T) do not activate singing behavior nor promote growth of song control nuclei to the same extend in male and female canaries (Serinus canaria). Because T acts in part via aromatization into an estrogen and brain aromatase activity is lower in females than in males, we hypothesized that this enzymatic difference explains the differential response to T in the two sexes. To test this idea, three groups of castrated males and 3 groups of photoregressed females received either 2 empty 10 mm Silastic implants or one empty implant and one implant filled with T or one implant filled with T plus one with estradiol (E2). Songs were recorded and analyzed for 3 hours each week for 6 weeks before brains were collected and song control nuclei volumes were measured in Nissl-stained sections. We confirmed that multiple measures of song were induced more efficiently by T in males than in females. Co-administration of E2 did notimprove these measures and even inhibited some measures such as song rate and song duration. Similarly, the volume of three main song control nuclei (HVC, RA, and Area X) was increased by the two steroid treatments but they remained significantly smaller in females than in males irrespective of the endocrine condition. The lower response of females to T is thus not caused by a lower aromatization of the steroid; sex differences in canaries are probably organized either by early steroid action or by sex-specific gene regulation directly in the brain. [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 cyclo-oxygenase inhibition on embryonic microglia and the sexual differentiation of the brain and behavior of Japanese quail (Coturnix japonica)
Delage, Charlotte ULiege; Nys, Gwenaël ULiege; Fillet, Marianne ULiege et al

in Hormones and Behavior (2021), 134

Enduring sex differences in the brain are established during a developmental process known as brain sexual differentiation and are mainly driven by estrogens during a critical period. In rodents, the ... [more ▼]

Enduring sex differences in the brain are established during a developmental process known as brain sexual differentiation and are mainly driven by estrogens during a critical period. In rodents, the masculinization of the preoptic area by estrogens derived from the central aromatization of testosterone depends in part on the interaction between microglia and prostaglandin E2 (PGE2), a pro-inflammatory hormone of the prostanoid subclass. In contrast, in birds, estrogens produced by females induce a demasculinization, but whether an interaction with the neuro-immune system is involved in this process is unknown. This study addressed this question by testing the effects of blockade of cyclo-oxygenases (COX), the rate-limiting enzymes for prostanoid synthesis, on embryonic microglia and the sexual differentiation of brain and behavior using the Japanese quail as an animal model. The results show that COX inhibition does not affect the behavior of females, but impairs male sexual behavior and suppresses the sex difference in microglial profiles at embryonic day 12 (E12) in the medial preoptic nucleus by increasing the number of microglia in males only. However, neither prostanoid concentrations nor PGE2 receptors differed between sexes in the hypothalamus and preoptic area (HPOA) during development. Overall, these results uncovered a potential role of prostanoids in the demasculinization of Japanese quail. Moreover, the parallel effect of COX inhibition on behavior and microglia suggests an interaction between prostanoids and microglia in brain demasculinization, thus fueling the hypothesis of a conserved role of the neuroimmune system in the organization of the brain by estrogens. [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

in Behavioural Brain Research (2021), 410

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 detailDNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon
Diddens, Jolien; Coussement, Louis; Frankl-Vilches, Carolina et al

in Frontiers in Cell and Developmental Biology (2021), 9

Song learning in zebra finches (Taeniopygia guttata) is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized ... [more ▼]

Song learning in zebra finches (Taeniopygia guttata) is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development. DNA methylation was very low, yet increased over time, particularly in song control nuclei. Only a small fraction of the massive differential expression in the developing zebra finch telencephalon could be explained by differential CpG and CpH DNA methylation. However, a strong association between DNA methylation and age-dependent gene expression was found for various transcription factors (i.e., OTX2, AR, and FOS) involved in neurodevelopment. Incomplete dosage compensation, independent of DNA methylation, was found to be largely responsible for sexually dimorphic gene expression, with dosage compensation increasing throughout life. In conclusion, our results indicate that DNA methylation regulates neurodevelopmental gene expression dynamics through steering transcription factor activity, but does not explain sexually dimorphic gene expression patterns in zebra finch telencephalon. [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 detailEstrogen-dependent sex difference in microglia in the developing brain of Japanese quail (Coturnix japonica)
Delage, Charlotte ULiege; Cornil, Charlotte ULiege

in Developmental Neurobiology (2020), 80(7-8), 239-262

Brain sexual differentiation is a developmental process leading to the establishment of stable neural sex differences. In birds and rodents, this process is largely driven by estrogens during a critical ... [more ▼]

Brain sexual differentiation is a developmental process leading to the establishment of stable neural sex differences. In birds and rodents, this process is largely driven by estrogens during a critical period. In rodents, estrogens drive the masculiniza- tion of the brain, a process that partly depends on microglia. In contrast, in birds, estrogens produced by females induce demasculinization, but whether microglia are involved in this process is unknown. This study assessed whether microglial num- ber, morphology, and/or activity differ between the sexes in selected regions of the developing quail brain and whether they are influenced by estrogens. We found a robust female-biased sex difference in microglial numbers between embryonic day 9 and 12 in the medial preoptic nucleus (POM), a key region for the expression of male sexual behavior. This difference relies on estrogens produced during the sensitive period. Although most embryonic microglia express iNOS, the expression of iNOS in individual microglia does not differ between sexes. Finally, microglial number and the expression of iNOS were not affected by the microglia inhibitor minocycline. Together, these results revealed an estrogen-dependent sex difference in microglia during the critical period for the sexual differentiation of the quail brain. This differ- ence mirrors the different role of estrogens in the development of birds and rodents and suggests a role for microglia in the sexual differentiation of the brain of birds, as in rodents, thus supporting the hypothesis of a conserved role of the neuroimmune system in the organization of the brain by estrogens. [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 detailConsequences of temperature-induced sex reversal on hormones and brain in Nile tilapia (Oreochromis niloticus)
Dussenne, Mélanie ULiege; Gennotte, Vincent ULiege; Rougeot, Carole ULiege et al

in Hormones and Behavior (2020), 121

Fish present a wide variety of sex determination systems ranging from strict genetic control (genetic sex de- termination, GSD) to strict environmental control (environmental sex determination, ESD ... [more ▼]

Fish present a wide variety of sex determination systems ranging from strict genetic control (genetic sex de- termination, GSD) to strict environmental control (environmental sex determination, ESD). Temperature is the most frequent environmental factor influencing sex determination. Nile tilapia (Oreochromis niloticus) is char- acterized by GSD with male heterogamety (XY/XX), which can be overridden by exposure to high masculinizing temperatures. Sex reversed Nile tilapia (XX males; neomales) have been described in the wild and seem un- distinguishable from XY males, but little is known about their physiology. The consideration of climate change urges the need to understand the possible physiological and behavioral consequences of such a sex reversal. The present study compared XX females, XY males and XX neomales for testis maturation, circulating sex -steroid concentrations as well as the size and number of neurons expressing arginine-vasotocin [AVT] and gonadotropin releasing hormone [GnRH] which are involved in sociosexual pathways. The results revealed that temperature- induced sex reversal does not affect testis maturation nor circulating sex steroid concentrations. Neomales show dramatically fewer GnRH1-immunoreactive (-ir) neurons than males and females, despite the observed normal testis physiology. Neomales also present fewer AVT-ir neurons in the magnocellular preoptic area than females and bigger AVT-ir neurons in the parvocellular POA (pPOA) compared to both males and females. The absence of consequences of sex reversal on testis development and secretions despite the reduced numbers of GnRH1 neurons suggests the existence of compensatory mechanisms in the hypothalamic-pituitary-gonadal axis, while the larger pPOA AVT neurons might predict a more submissive behavior in neomales. [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 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 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 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 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 detailRole for the Membrane Estrogen Receptor alpha in the sexual differentiation of the brain
Khbouz, Badr ULiege; de Bournonville, Catherine ULiege; Court, Lucas ULiege et al

in European Journal of Neuroscience (2020), 52(1), 2627-2645

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best characterized responses activated by ... [more ▼]

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best characterized responses activated by estrogens in adulthood and largely depend on ERα. Evidence exists that nucleus‐ and membrane‐initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both in short‐ and long‐term. However, questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated responses. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site, which prevents membrane ERα signaling (mERα□□ERα□C451A), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no genotype effect on the expression of female sexual behavior, while male sexual behavior was significantly reduced, but not abolished, in males homozygous for the mutation. Similarly, the number of kisspeptin‐ (Kp‐ir) and calbindin‐immunoreactive (Cb‐ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually‐dimorphic nucleus of the preoptic area (SDN‐POA), respectively, were not different between genotypes in females. In contrast, homozygous males showed increased numbers of Kp‐ir and decreased numbers of Cb‐ir neurons compared to wild‐types, thus leading to an intermediate phenotype between females and wild‐type males. Importantly, females neonatally treated with estrogens exhibited the same neurochemical phenotype as their corresponding genotype among males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain. [less ▲]

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See detailMEMBRANE ESTROGEN RECEPTOR ALPHA PARTICIPATES IN THE ORGANIZATION OF THE BRAIN BY PERINATAL ESTROGENS
Cornil, Charlotte ULiege; Khbouz, Badr ULiege; Court, Lucas ULiege et al

Conference (2019, May 21)

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behaviors in rodents constitute some of the best characterized responses activated by ... [more ▼]

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behaviors in rodents constitute some of the best characterized responses activated by estrogens in adulthood and largely depend on estrogen receptor alpha (ERα). Evidence exists that nucleus- and membrane-initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both short- and long-term. However questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated endpoints. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site which invalidates membrane ER signaling (mERα), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no effect of genotype on the expression of female sexual behavior while male sexual behavior was significantly reduced but not impaired in males homozygous for the mutation. Similarly, the number of kisspeptin- (Kp-ir) and calbindin-immunoreactive (Cb-ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually-dimorphic nucleus of the preoptic area (SDN-POA) respectively were not different between genotypes in females, while homozygous males showed an increased number of Kp-ir and a decreased number of Cb-ir neurons compared to their wild-type littermates thus leading to an intermediate phenotype between females and wild-type males. Importantly, females treated with estrogens between post-natal day 0 and 5 exhibited the same neurochemical phenotype as their corresponding genotype in males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain. [less ▲]

Detailed reference viewed: 94 (16 ULiège)