Charlotte Cornil

University of Liège | ulg · GIGA-Neurosciences Unit

Many species, including humans exhibit a wide range of social behaviors that are crucial for the adaptation and survival of most species. Brain organization and function are shaped by genetic and environmental factors, although their precise contributions have been relatively understudied in the context of artificial selection. We used divergent li...

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E 4 ) a natural estrogen act...

Vertebrates, including humans exhibit a wide range of social behaviors that are crucial for the adaptation and survival of most species. The brain organization and function are shaped by genetic and environmental factors, although their precise contributions have been poorly explored in the context of artificial selection. We used divergent lines o...

The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge. Declining fertility rates together with rising incidence rates of reproductive disorders and other endocrine-related diseases underscores the urgency in taking more action. Addressing the...

The activation of male sexual behavior depends on brain estrogen synthesis. Estrogens act through nuclear and membrane receptors producing effects within hours/days or seconds/minutes, respectively. In mice, estrogen receptor alpha (ERα) is the main estrogen receptor (ER) controlling the activation of male sexual behavior. Although neuroestrogens r...

Behavioral neuroendocrinology has largely relied on mammalian models to understand the relationship between hormones and behavior, even if this discipline has historically used a larger diversity of species than other fields. Recent advances revealed the potential of avian models in elucidating the neuroendocrine bases of behavior. This paper provi...

Background Behavioral sex differences are widespread in the animal world. These differences can be qualitative (i.e., behavior present in one sex but not the other, a true sex dimorphism) or quantitative (behavior is present at a higher rate or quality in one sex compared to the other). Singing in oscine songbirds is associated with both types of d...

We previously confirmed that effects of testosterone (T) on singing activity and on the volume of brain song control nuclei are sexually differentiated in adult canaries: females are limited in their ability to respond to T as males do. Here we expand on these results by focusing on sex differences in the production and performance of trills, i.e.,...

The song control nucleus HVC of songbirds has emerged as a widespread model system to study adult neurogenesis and the factors that modulate the incorporation of new neurons, including seasonal state, sex differences or sex steroid hormone concentrations. However, the specific function of these new neurons born in adulthood remains poorly understoo...

We previously confirmed that effects of testosterone (T) on singing activity and on the volume of brain song control nuclei are sexually differentiated in adult canaries: females are limited in their ability to respond to T as males do. Here we expand on these results by focusing on sex differences in the production and performance of trills, i.e.,...

Background. Behavioral sex differences are widespread in the animal world. These differences can be qualitative (i.e., behavior present in one sex but not the other, a true sex dimorphism) or quantitative (behavior is present at a higher rate or quality in one sex compared to the other). Singing in oscine songbirds is associated with both types of...

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling is unclear. To address this question, we used two complementary approaches: estetrol (E4) a natural estrogen described to act as an agonist of nuclear ERα and...

The song control nucleus HVC of songbirds has emerged as a widespread model system to study adult neurogenesis and the factors that modulate the incorporation of new neurons, including seasonal state, sex differences or sex steroid hormone concentrations. However, the specific function of these new neurons born in adulthood remains poorly understoo...

Jacques Balthazart is a Belgian behavioral neuroendocrinologist whose work focused on the neuroendocrineNeuroendocrine regulation of reproductive behaviorsBehaviors of birdsBirds, primarily based on studies in Japanese quailQuail and songbirds. He is best known for his studies of the organizational and activational actions of sex steroidsSex steroi...

The binding of 17β-oestradiol to oestrogen receptor alpha (ERα) plays a crucial role in the control of reproduction, acting through both nuclear and membrane-initiated signalling. To study the physiological role of membrane ERα in the reproductive system, we used the C451A-ERα mouse model with selective loss of function of membrane ERα. Despite C45...

Temperate-zone birds display marked seasonal changes in reproductive behaviors and the underlying hormonal and neural mechanisms. These changes were extensively studied in canaries (Serinus canaria) but differ between strains. Fife fancy male canaries change their reproductive physiology in response to variations in day length but it remains unclea...

Adult treatments with testosterone (T) do not activate singing behavior nor promote growth of song control nuclei to the same extent 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 in many vertebrates, we hypothesized that this en...

In some fish species, sex is determined by the combination of genetic and environmental factors. In most species concerned, extreme temperatures during the sensitive period of sex differentiation drives masculinization, independently of the female sex chromosomes. In Nile tilapia (XY male heterogamety), XX juveniles exposed to high temperatures (>3...

In male Japanese quail, brain aromatase is crucial for the hormonal activation of sexual behavior, but the sites producing neuro‐estrogens critical for these behaviors have not been completely identified. This study examined the function of aromatase expressed in several nuclei of the social behavior network on a measure of sexual motivation known...

This short review focuses on the mechanisms of action of brain derived estrogens, or neuroestrogens on male sexual behavior, one of the best characterized examples of estrogen synthesis/action on behavior. After summarizing the modes of regulation of estrogen synthesis and action in the context of this behavior, we identify questions remaining in o...

Classically, estrogens regulate male sexual behavior through effects initiated in the nucleus. However, neuroestrogens, i.e., estrogens locally produced in the brain, can act within minutes via membrane-initiated events. In male quail, rapid changes in brain aromatase activity occur after exposure to sexual stimuli. We report here that local extrac...

Songbirds learn their vocalizations during developmental sensitive periods of song memorization and sensorimotor learning. Some seasonal songbirds, called open-ended learners, recapitulate transitions from sensorimotor learning and song crystallization on a seasonal basis during adulthood. In adult male canaries, sensorimotor learning occurs each y...

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 mi...

Songbirds learn their vocalizations during sensitive periods of song memorization and sensorimotor learning during development. Some seasonal songbirds, called open-ended learners, recapitulate transitions from sensorimotor learning and song crystallization on a seasonal basis during adulthood. In adult male canaries, sensorimotor learning occurs e...

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-depen...

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 fin...

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 masculinization of the brain, a process that partly depends on microglia. In contrast, in birds, estrogens...

Estrogens play a key role in the sexual differentiation of the brain and behavior. While early estrogen actions exert masculinizing effects on the male brain of rodents, a diametrically opposite effect is observed in birds where estrogens demasculinize the female brain. Yet, the two vertebrate classes express similar sex differences in the brain an...

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 (FI...

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...

Fish present a wide variety of sex determination systems ranging from strict genetic control (genetic sex determination, GSD) to strict environmental control (environmental sex determination, ESD). Temperature is the most frequent environmental factor influencing sex determination. Nile tilapia (Oreochromis niloticus) is characterized by GSD with m...

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 ac...

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 p...

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 vis...

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 o...

Seasonal timing of reproduction is a key life-history trait, but we know little about the mechanisms underlying individual variation in female endocrine profiles associated with reproduction. In birds, 17β-oestradiol is a key reproductive hormone that links brain neuroendocrine mechanisms, involved in information processing and decision-making, to...

In male songbirds, the motivation to sing is largely regulated by testosterone (T) action in the medial preoptic area, whereas T acts on song control nuclei to modulate aspects of song quality. Stereotaxic implantation of T in the medial preoptic nucleus (POM) of castrated male canaries activates a high rate of singing activity, albeit with a longe...

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 impl...

Testosterone activates singing within days in castrated male songbirds but full song quality only develops after a few weeks. Lesions of the medial preoptic nucleus (POM) inhibit while stereotaxic testosterone implants into this nucleus increase singing rate suggesting that this site plays a key role in the regulation of singing motivation. Testost...

Both systemic and local production contribute to the concentration of steroids measured in the brain. This idea was originally based on rodent studies and was later extended to other species including humans and birds. In quail, a widely used model in behavioral neuroendocrinology, it was demonstrated that all enzymes needed to produce sex steroids...

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 c...

Japanese quail belong to the order Galliformes and the family Phasianidae. They are thought to be indigenous to East Asia including Japan, China, and Korea. Japanese quail are characterized by their small size, with an average weight between 200 and 300 g depending on their strain and sex. This chapter illustrates how Japanese quail can be used to...

The appearance of perineuronal nets (PNNs) represents one of the mechanisms that contribute to the closing of sensitive periods for neural plasticity. This relationship has mostly been studied in the ocular dominance model in rodents. Previous studies also indicated that PNN might control neural plasticity in the song control system of songbirds. T...

In seasonally breeding songbirds such as canaries, singing behavior is predominantly under the control of testosterone and its metabolites. Short daylenths in the fall that break photorefractoriness are followed by increasing daylengths in spring that activate singing via both photoperiodic and hormonal mechanisms. However, we observed in a group o...

Sex steroid hormones act during early development to shape the circuitry upon which these same hormones act in adulthood to control behavioral responses to various stimuli. The "organizational" vs. "activational" distinction was proposed to explain this temporal difference in hormone action. In both of these cases steroids were thought to act genom...

Estrogens exert pleiotropic effects on multiple physiological and behavioral traits including sexual behavior. These effects are classically mediated via binding to nuclear receptors and subsequent regulation of target gene transcription. Estrogens also affect neuronal activity and cell-signaling pathways via faster, membrane-initiated events. Alth...

The ovaries are often thought of as the main and only source of estrogens involved in the regulation of female behavior. However, aromatase, the key enzyme for estrogen synthesis, although it is more abundant in males, is expressed and active in the brain of females where it is regulated by similar mechanisms as in males. Early work had shown that...

In male quail, estrogens produced in the brain (neuroestrogens) exert a dual action on male sexual behavior: they increase sexual motivation within minutes via mechanisms activated at the membrane but facilitate sexual performance by slower, presumably nuclear-initiated, mechanisms. Recent work indicates that neuroestrogens are also implicated in t...

Aromatase inhibitors, which are widely used for the treatment of estrogen-dependent cancers, have been associated with psychiatric side effects ranging from mania to depression. In the present study, we investigated sex differences in the behavioral and neurochemical effects of aromatase inhibition on male and female, sham-operated or gonadectomize...

Le 17β-œstradiol (E2) est une hormone sexuelle féminine ayant un rôle majeur dans les fonctions de reproduction, agissant au niveau de l’axe hypothalamo-hypophysaire gonadique sur le récepteur des œstrogènes ERα, contrôlant ainsi finement les différentes phases du développement du follicule ovarien au cours du cycle œstral. Un dérèglement de ces no...

Estrogens derived from brain testosterone aromatization (neuro-estrogens) are critical for the activation of male sexual behavior. Their effects on this behavior are typically associated with long-term changes in circulating levels of testosterone and the transcriptional activity of their liganded nuclear receptors. According to this view, neuro-es...

In Nile tilapia Oreochromis niloticus, phenotypic males and females with different sexual genotypes (XX, XY, YY) have particular behavioral and physiological traits. Compared to natural XX females and XY males, XY and YY females and XX males expressed higher level of aggressiveness that could be related to higher levels of 17β-estradiol and 11-keto...

It is increasingly recognized that brain-derived estrogens (neuroestrogens) can regulate brain physiology and behavior much faster than what was previously known from the transcriptional action of estrogens on nuclear receptors. One of the best examples of such neuromodulation by neuroestrogens concerns the acute regulation of sensory coding by the...

Perineuronal nets (PNN) are aggregations of chondroitin sulfate proteoglycans surrounding the soma and proximal processes of neurons, mostly GABAergic interneurons expressing parvalbumin. They limit the plasticity of their afferent synaptic connections. In zebra finches PNN develop in an experience-dependent manner in the song control nuclei HVC an...

Estrogens are known to act rapidly, probably via membrane estrogen receptors, to induce fast effects on physiological and behavioral processes. Engaging in some of these behaviors, such as sexual behavior, results in an acute modulation of the production of estrogens in the brain by regulating the efficiency of the estrogen synthase enzyme, aromata...

In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, impl...

Final full data set. (XLSX)

Testosterone plays a key role in the control of seasonal changes in singing behavior and its underlying neural circuitry. After administration of exogenous testosterone, song quality and song control nuclei volumes change over the course of weeks, but song rate increases within days. The medial preoptic nucleus (POM) controls sexual motivation and...

The zebra finch (Taeniopygia guttata) song control system consists of several series of interconnected brain nuclei that undergo marked changes during ontogeny and sexual development, making it an excellent model to study developmental neuroplasticity. Despite the demonstrated influence of hormones such as sex steroids on this phenomenon, thyroid h...

The avian brain is both a target and a source of estrogens. The rapid effects of estrogens on avian social behavior have been studied extensively in both captive and free-living birds. Here we present accumulated evidence that brain estrogens regulate avian social behaviors. Fast changes in neuroestrogens occur during sexual behavior, aggression, a...

Estradiol (E2) is a key regulator of reproduction through its role on the feedback control of gonadotropin secretion by the hypothalamus. E2 effects are mainly mediated via estrogen receptor alpha (ERα) activation by a combination of the nuclear and the membrane-associated pathways. However, the contribution of these mechanisms to the regulation of...

Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In av...

Zebra finches are an excellent model to study the process of vocal learning, a complex socially-learned tool of communication that forms the basis of spoken human language. So far, structural investigation of the zebra finch brain has been performed ex vivo using invasive methods such as histology. These methods are highly specific, however, they s...

Recent evidence has implicated steroid hormones, specifically estrogens, in the rapid modulation of cognitive processes. Songbirds have been a useful model system in the study of complex cognitive processes including birdsong, a naturally learned vocal behavior regulated by a discrete steroid sensitive telencephalic circuitry. Singing behavior is k...

Although aromatase is expressed in both male and female brains, its functional significance in females remains poorly understood. In female quail, sexual receptivity is activated by estrogens. However it is not known whether sexual motivation is similarly estrogen-dependent and whether estrogens locally produced in the brain contribute to these beh...

Estradiol (E2) can act in the brain in a relatively fast manner (i.e., seconds to minutes) usually through signaling initiated at the cell membrane. Brain-derived E2 has thus been considered as another type of neurotransmitter. Recent work found that behaviors indicative of male sexual motivation are activated by estrogenic metabolites of testoster...

Large morphological sex differences in the vertebrate brain were initially identified in song control nuclei of oscines. Besides gross differences between volumes of nuclei in males and females, sex differences also concern the size and dendritic arborization of neurons and various neurochemical markers, such as the calcium-binding protein parvalbu...

Estrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17β-estradiol is synthesized by the enzyme aromatase, using testosterone a...

Various studies in rodents recently concluded that puberty should be considered as a second period of organization of brain and behavior and that action of sex steroids at that time is long lasting and possibly permanent. We tested this notion in male Japanese quail that had been castrated before 3 weeks post-hatch by analyzing whether a similar tr...

Jacques Balthazart will reach the age of 65 next year on June 29, 2014 and according to the Belgian rules will have to retire from all his official functions at the University of Liege, though he is not planning to end his scientific career at this point. On this occasion, we would like to celebrate with him and organize an International Conference...

Estradiol-17β (E2) synthesized in the brain plays a critical role in the activation of sexual behavior in many vertebrate species. Because E2 concentrations depend on aromatization of testosterone, changes in aromatase enzymatic activity (AA) are often utilized as a proxy to describe E2 concentrations. Utilizing two types of stimuli (sexual interac...

Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by small-conductance Ca(2+) -activated K(+) (SK) channels. Recent ex vivo and in vivo experiments have suggested that SK channel blockade increases the firing rate and/or bursting in these neurons. The purpose of this study was therefore t...

Numerous steroid hormones, including 17β-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 co...

Oestrogens activate nucleus- and membrane-initiated signalling. Nucleus-initiated events control a wide array of physiological and behavioural responses. These effects generally take place within relatively long periods of time (several hours to days). In contrast, membrane-initiated signalling affects a multitude of cellular functions in a much sh...

It is increasingly recognized that estrogens produce rapid and transient effects at many neural sites ultimately impacting physiological and behavioral endpoints. The ability of estrogens to acutely regulate cellular processes implies that their concentration should also be rapidly fine-tuned. Accordingly, rapid changes in the catalytic activity of...

Sexual behavior can be usefully parsed into an appetitive and a consummatory component. Both appetitive and consummatory male-typical sexual behaviors (respectively, ASB and CSB) are activated in male Japanese quail by testosterone (T) acting in the medial preoptic nucleus (POM), but never observed in females. This sex difference is based on a dema...