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See detailThe organization and activation of sexual behavior in quail
Cornil, Charlotte ULiege

in Ludwig, Mike; Levkowitz, Gil (Eds.) Model animals in neuroendocrinology: From worm to mouse to man (in press)

Japanese quail are small galliformes, easily raised and maintained in laboratory settings. As their behavior is tightly regulated by sex steroid hormones, they constitute the most studied avian species ... [more ▼]

Japanese quail are small galliformes, easily raised and maintained in laboratory settings. As their behavior is tightly regulated by sex steroid hormones, they constitute the most studied avian species for the hormonal regulation of sexual behavior. They were used to establish the hormonal specificity of this regulation, to map the brain regions involved in behavior control and to demonstrate the key role of brain aromatization of testosterone in the regulation of male sexual behavior. As the quail brain expresses large amounts of aromatase, the key enzyme for the conversion androgens into estrogens, Japanese quail constitutes an exquisite model to study the role and control mechanisms of this enzyme both in vitro and in vivo. Work conducted in quail contributed to show that along with the long-term regulation of the expression of aromatase by sex steroids, its activity is also rapidly regulated by neuronal activity. More recently, work in quail unraveled a role for brain aromatase in the regulation of female sexual behavior. Finally, Japanese quail have been used to study how sex steroid hormones contribute to the emergence and maintenance of sex differences in brain and behavior. In particular, as the embryo develops outside the mother’s womb, they constitute a suitable model to distinguish between the direct effects of hormonal treatments and their influence through modulation of the maternal environment. Most techniques classically employed in neuroscience and neuroendocrinology have been adapted to this species and more modern techniques such as transgenesis and viral transfection,are now becoming available as well thus expanding the possibilities offered by this model. [less ▲]

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See detailDual action of neuro-estrogens in the regulation of male sexual behavior
Cornil, Charlotte ULiege; de Bournonville, Catherine

in General and Comparative Endocrinology (2018), 256

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 ... [more ▼]

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-estrogens would prime the neural circuits controlling the long-term expression of behavior, which would then be acutely regulated by neurotransmitter systems conveying information from the social environment. In parallel, neuro-estrogens are also able to produce much faster effects than previously anticipated. Our recent investigations in Japanese quail revealed an interesting dichotomy in the regulation of male sexual behavior by membrane- and nuclear-initiated estrogen signaling providing respectively an acute modulation of sexual motivation and a long-term control of the capacity to display the copulatory sequence. In parallel, a similar dichotomy applies to the regulation of brain aromatase whose expression depends on the transcriptional activity of testosterone metabolites while its enzymatic activity is rapidly regulated in a region- and context-dependent manner. Recent evidences suggest that rapid changes in sexual motivation result from rapid changes in local estrogen production. Together, these data support the idea that the acute regulation of some aspects of male sexual behavior depends not only on classical neurotransmitter systems, but also on rapid and spatially restricted changes in local estrogen availability. The existing literature suggests that this acute regulation by neuro-estrogens of the motivational aspects of behavior could be generalized to other systems such as singing behavior in songbirds. [less ▲]

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See detailOn the role of brain aromatase in females: why are estrogens produced locally when they are available systemically?
Cornil, Charlotte ULiege

in Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural and Behavioral Physiology (2018), 204

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 ... [more ▼]

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 estrogens produced in the ventromedial hypothalamus are involved in the regulation of female sexual behavior in musk shrews. However, the question of the role of central aromatase in general had not received much attention until recently. Here, I will review the emerging concept that central aromatization plays a role in the regulation of physiological and behavioral endpoints in females. The data support the notion that in females, brain aromatase is not simply a non-functional evolutionary vestige, and provide support for the importance of locally produced estrogens for brain function in females. These observations should also have an impact for clinical research. © 2017 Springer-Verlag GmbH Germany [less ▲]

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See detailSex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats.
Kokras, N; Pastromas, N; Papasava, D et al

in Psychoneuroendocrinology (2018), 87

Aromatase inhibitors, which are widely used for the treatment of estrogen-dependent cancers, have been as- sociated with psychiatric side effects ranging from mania to depression. In the present study, we ... [more ▼]

Aromatase inhibitors, which are widely used for the treatment of estrogen-dependent cancers, have been as- sociated 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 gonadectomized adult rats. Three weeks after surgery, rats received chronic treatment with the aromatase inhibitor letrozole or vehicle and were then subjected to the open field test, which assesses general activity. Half of the subjects were subsequently exposed to the stressful procedure of the forced swim test (FST), which is also a test of antidepressant activity. Aromatase activity was analyzed in the hypothalamus and tes- tosterone and corticosterone were assayed in the blood serum of all rats. The hippocampus and prefrontal cortex (PFC) were analyzed for monoamine (noradrenaline, dopamine and serotonin), as well as amino acid (GABA, glutamate, glycine, taurine, alanine and histidine) levels. The observed decrease in hypothalamic aromatase activity confirmed the efficacy of letrozole treatment in both sexes. Moreover, letrozole enhanced testosterone levels in sham-operated females. In the open field test, females were overall more active and explorative than males and gonadectomy eliminated this sex difference. In the FST, females exhibited overall higher immobility than males and gonadectomy further enhanced this passive behavior in both sexes. However, sustained ar- omatase inhibition had no effect on open field and FST behaviors. Head shakes during FST, which were fewer in females than in males, were reduced by castration in males and by letrozole treatment in ovariectomized fe- males, suggesting a role of testosterone and extra-gonadal estrogens in the expression of this behavior. Sustained aromatase inhibition also decreased noradrenaline and the dopaminergic turnover rates [DOPAC/DA, HVA/DA] in the hippocampus and PFC of male and female rats, irrespectively of gonadectomy. Moreover, letrozole treatment enhanced the serotonergic turnover [5HIAA/5HT] rate in the hippocampus of males and females, irrespectively of gonadectomy. Amino acid levels were not influenced by letrozole, but sex differences were demonstrated with higher levels in the PFC of females vs. males. Present findings suggest that the neu- ropsychiatric effects of aromatase inhibition can be attributed to the inhibition of extragonadal estrogen synthesis, presumably in the brain, and could be further associated with serotonergic and catecholaminergic changes in brain regions involved in mood and cognition. Importantly, present data could be linked with the neurobiology of affective side-effects in post-menopausal women receiving aromatase inhibitors. [less ▲]

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See detailRapid changes in preoptic estradiol concentration during male sexual behavior
de Bournonville, Marie-Pierre ULiege; de Bournonville, Catherine; Ball, Gregory et al

Poster (2017, November 11)

Estrogens such as estradiol (E2) exert pleiotropic effects on physiological and behavioral responses such as neuroprotection, aggression or reproduction. Estrogens derived from local brain synthesis ... [more ▼]

Estrogens such as estradiol (E2) exert pleiotropic effects on physiological and behavioral responses such as neuroprotection, aggression or reproduction. Estrogens derived from local brain synthesis (neuroestrogens) are critical for the regulation of different functions including the control of male sexual behavior. Classically, E2 acts through effects initiated in the nucleus to regulate male sexual function. Along with these long-term effects, E2 also acts rapidly (within minutes) via membrane-initiated events. These effects are thought to depend on short-term variations in the local production of estrogens, through rapid fluctuations of the enzymatic activity of brain aromatase. In Japanese quail, rapid modulations of brain aromatase activity (AA) have been reported after sexual interactions or exposure to an acute stress. These changes take place mainly in the medial preoptic nucleus (POM), a sexually differentiated structure that plays a key role in the control of male sexual behavior and where aromatase is densely expressed. Yet, it has recently been shown that, in the short term, AA does not always reflect local E2 concentration. This study was designed to determine by in vivo microdialysis whether local E2 concentrations fluctuate during sexual interactions and test whether these changes parallel the decrease in AA observed ex vivo after copulation. We first conducted a series of experiments to validate the microdialysis and E2 assay. When dialysis probes were placed in successive baths containing known increasing amounts of E2, proportional changes in E2 concentration were measured in the dialysate. Moreover, a rise in E2 concentration was detected after in vivo retrodialysis of testosterone only if the probe was located within the POM and, after a peripheral injection of E2, a sharp rise of E2 was detected regardless of the probe location. Together these results show that in vivo microdialysis is a valid method to assess endogenous fluctuations of brain E2 concentrations in behaving animals. Two independent experiments then identified a rise in E2 concentrations in POM during sexual interactions. This increase occurred within 10 min after the initiation of the sexual interaction and was specific to the POM as there was no increase in E2 concentrations in males that had their cannula outside of this area. Together these data confirm that rapid changes in AA measured ex vivo cannot be considered as a reliable proxy for E2 concentrations. The discrepancies could originate either from the different time resolution related to the two techniques or from differences in the microenvironment in which aromatase functions in vivo and during ex vivo assays. [less ▲]

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See detailChanges in preoptic estradiol concentrations during male sexual behavior
de Bournonville, Marie-Pierre ULiege; de Bournonville, Catherine; Ball, Gregory et al

in Frontiers in Neuroscience (2017, May 30)

Besides its long-term control by steroids, male sexual behavior is also modulated by membrane-initiated effects of neuroestrogens in the short-term (within minutes). These effects are thought to depend on ... [more ▼]

Besides its long-term control by steroids, male sexual behavior is also modulated by membrane-initiated effects of neuroestrogens in the short-term (within minutes). These effects are thought to depend on short-term variations in the local production of estrogens, through rapid fluctuations of the enzymatic activity of brain aromatase, the enzyme that synthesizes estradiol (E2) from testosterone. Studies in male Japanese quail have shown that a sexual interaction with a female leads to a decrease in the activity of brain aromatase within minutes. These effects occur mainly within the medial preoptic nucleus (POM), a sexually dimorphic structure of the preoptic area that plays a key role in the activation of male sexual behavior and contains the highest aromatase activity (AA) in the brain. However recent studies showed that AA does not always reflect local E2 concentration. For example, while an acute stress decreases AA in the POM, E2 concentration increases in the same conditions. Here we used in vivo microdialysis to quantify changes in E2 concentration in the male POM during sexual interactions with a female. A series of experiments conducted to validate the in vivo dialysis and RIA methods showed that (1) E2 concentration in the dialysate change linearly with the concentration of a bath containing known amounts of E2 in which the probe was placed, (2) an increase in preoptic E2 concentration is observed after retrodialysis of testosterone and (3) preoptic E2 levels also increase after a peripheral injection of E2. Together these results suggest that in vivo dialysis is a suitable method to assay E2 in the range of brain concentrations suspected to be present in physiological conditions. With this approach, we showed during two independent experiments that E2 concentrations increase in the POM during sexual interactions with a female. Birds that had their cannula placed outside the POM did not show any increase in E2 levels. The E2 increase in the POM could serve to maintain motivation during the entire sexual encounter. The decrease of AA observed ex vivo after copulation would then reflect a compensatory mechanism to restore baseline pre-copulatory conditions. [less ▲]

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See detailPerineuronal nets and song learning-related neuroplasticity in the songbird brain
Cornez, Gilles ULiege; Jonckers, Elisabeth; Schevchouk, Olesya et al

Conference (2017, May 22)

Perineuronal nets (PNN) are aggregations of extracellular matrix components surrounding the soma of some neurons, mainly GABAergic interneurons expressing the calcium binding protein parvalbumin (PV+). In ... [more ▼]

Perineuronal nets (PNN) are aggregations of extracellular matrix components surrounding the soma of some neurons, mainly GABAergic interneurons expressing the calcium binding protein parvalbumin (PV+). In mammals, the development of PNN limits synaptogenesis around PV+ neurons and PNN have been validated as a marker characterizing the end of critical periods for visual learning. In songbirds, song learning is limited to critical periods during ontogeny in close-ended learners such as zebra finches and to specific phases of the annual cycle in open-ended learners such as canaries that are able to modify their song seasonally. Sensitive periods for song learning are associated with neuroplasticity including morphological changes due to neurogenesis and synaptic reorganization in the song control nuclei during development and adult seasonal song modifications. The hormonal control of developmental and seasonal neuroplasticity is well documented in songbirds but little is known about the possible regulation of sensitive periods for vocal learning by PNN. First, to explore the expression of PNN throughout the development, we used zebra finches brains collected at different key ages in the song learning process (10, 20, 30, 40, 50, 60, 90, 120 days post-hatch, dph) and we quantified PNN expression and their colocalization around PV+ interneurons. The number of PNN and the % of PNN around PV+ interneurons increased progressively during developmental song learning in 3 of the main song control nuclei (HVC, RA and Area X). Moreover, we confirmed that females that never sing have fewer PNN than males in HVC and RA, two song nuclei involved in song production, at all ages after the peak in PNN numbers seen in males between 50 and 90 dph. Secondly we used adult male and female canaries (in 2 different experiments) treated with a subcutaneous implant filled with testosterone or left empty in control subjects to mimic what happens in the spring when the seasonal modification of the song ends and the song crystallizes. Testosterone significantly increased the number of PNN in the main song control nuclei in both sexes. Together these data suggest that increased expression of PNN in the songbird brain might limit neuroplasticity at the end of developmental and seasonal vocal learning [less ▲]

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See detailChanges in preoptic estradiol and glutamate concentration in the preoptic area during male sexual behavior
Cornil, Charlotte ULiege

Scientific conference (2017, February 12)

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See detailPerineuronal nets and vocal plasticity in songbirds: a proposed mechanism to explain the difference between closed-ended and open-ended learning
Cornez, Gilles ULiege; Madison, F.N.; Van der Linden, A. et al

in Developmental Neurobiology (2017), 77(8), 975-994

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 ... [more ▼]

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 and RA (nucleus robustus arcopallialis) when young birds crystallize their song. Because songbird species that are open-ended learners tend to recapitulate each year the different phases of song learning until their song crystallizes at the beginning of the breeding season, we tested whether seasonal changes in PNN expression would be found in the song control nuclei of a seasonally breeding species such as the European starling. Only minimal changes in PNN densities and total number of cells surrounded by PNN were detected. However, comparison of the density of PNN and of PNN surrounding parvalbumin-positive cells revealed that these structures are far less numerous in starlings that show extensive adult vocal plasticity, including learning of new songs throughout the year, than in the closed-ended learner zebra finches. Canaries that also display some vocal plasticity across season but were never formally shown to learn new songs in adulthood were intermediate in this respect. Together these data suggest that establishment of PNN around parvalbumin-positive neurons in song control nuclei has diverged during evolution to control the different learning capacities observed in songbird species. This differential expression of PNN in different songbird species could represent a key cellular mechanism mediating species variation between closed-ended and open-ended learning strategies. [less ▲]

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See detailRapid changes in brain aromatase activity in the female quail brain following expression of sexual behaviour
de Bournonville, C.; Ball, G. F.; Balthazart, Jacques ULiege et al

in Journal of Neuroendocrinology (2017), 29(11),

In male quail, oestrogens produced in the brain (neuro-oestrogens) exert a dual action on male sexual behaviour: they increase sexual motivation within minutes via mechanisms activated at the membrane but ... [more ▼]

In male quail, oestrogens produced in the brain (neuro-oestrogens) exert a dual action on male sexual behaviour: 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 neuro-oestrogens are also implicated in the control of female sexual motivation despite the presence of high circulating concentrations of oestrogens of ovarian origin. Interestingly, aromatase activity (AA) in the male brain is regulated in time domains corresponding to the slow “genomic” and faster “nongenomic” modes of action of oestrogens. Furthermore, rapid changes in brain AA are observed in males after sexual interactions with a female. In the present study, we investigated whether similar rapid changes in brain AA are observed in females allowed to interact sexually with males. A significant decrease in AA was observed in the medial preoptic nucleus after interactions that lasted 2, 5 or 10 minutes, although this decrease was no longer significant after 15 minutes of interaction. In the bed nucleus of the stria terminalis, a progressive decline of average AA was observed between 2 and 15 minutes, although it never reached statistical significance. AA in this nucleus was, however, negatively correlated with the sexual receptivity of the female. These data indicate that sexual interactions affect brain AA in females as in males in an anatomically specific manner and suggest that rapid changes in brain oestrogens production could also modulate female sexual behaviour. © 2017 British Society for Neuroendocrinology [less ▲]

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See detailDo sex reversal procedures differentially affect agonistic behaviours and sex steroid levels depending on the sexual genotype in Nile tilapia?
Gennotte, Vincent ULiege; Akonkwa, Balagizi; Mélard, Charles ULiege et al

in Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology (2017), 327(4), 153-162

In Nile tilapia Oreochromis niloticus, phenotypic males and females with different sexual genotypes (XX, XY, YY) have particular behavioural and physiological traits. Compared to natural XX females and XY ... [more ▼]

In Nile tilapia Oreochromis niloticus, phenotypic males and females with different sexual genotypes (XX, XY, YY) have particular behavioural 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-oestradiol and 11-ketotestosterone respectively. Our results suggest that the presence of a Y chromosome increases aggressiveness in females. However, since the same relationship between aggressiveness and the Y chromosome is not observed in males, we can hypothesize that the differences in aggressiveness are not directly dependent on the genotype but on the sex reversal procedures applied on young fry during their sexual differentiation to produce these breeders. These hormonal treatments could have permanently modified the development of the brain and consequently influenced the behaviour of adults independently of their genotype. In both hypotheses (genotype or sex reversal influence), the causes of behavioural modifications have to be searched in an early modification of the brain sexual differentiation. [less ▲]

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See detailStudies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis.
Shevchouk, Olesya ULiege; Ball, G.F.; Cornil, Charlotte ULiege et al

in PLoS ONE (2017), 12(1), 0170938

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 ... [more ▼]

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, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β- estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. [less ▲]

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See detailExploring sex differences in the adult zebra finch brain: in vivo diffusion tensor imaging and ex vivo super-resolution track density imaging
Hamaide, J.; De Groof, G.; Van Steenkiste, G. et al

in NeuroImage (2017), 146

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 ... [more ▼]

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 strongly interfere with performing whole-brain analyses and exclude longitudinal studies aimed at establishing causal correlations between neuroplastic events and specific behavioral performances. Therefore, the aim of the current study was to implement an in vivo Diffusion Tensor Imaging (DTI) protocol sensitive enough to detect structural sex differences in the adult zebra finch brain. Voxel-wise comparison of male and female DTI parameter maps shows clear differences in several components of the song control system (i.e. Area X surroundings, the high vocal center (HVC) and the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which corroborate previous findings and are in line with the clear behavioral difference as only males sing. Furthermore, to obtain additional insights into the 3-dimensional organization of the zebra finch brain and clarify findings obtained by the in vivo study, ex vivo DTI data of the male and female brain were acquired as well, using a recently established super-resolution reconstruction (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked reduction in acquisition time without interfering with the (spatial and angular) resolution and SNR which enabled to acquire a data set characterized by a 78μm isotropic resolution including 90 diffusion gradient directions within 44h of scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic Track Density Imaging (TDI) was performed for the purpose of super resolved track density imaging, further pushing the resolution up to 40μm isotropic. The DTI and TDI maps realized atlas-quality anatomical maps that enable a clear delineation of most components of the song control and auditory systems. In conclusion, this study paves the way for longitudinal in vivo and high-resolution ex vivo experiments aimed at disentangling [less ▲]

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See detailTopography and Lateralized Effect of Acute Aromatase Inhibition on Auditory Processing in a Seasonal Songbird
de groof, Geert; Balthazart, Jacques ULiege; Cornil, Charlotte ULiege et al

in Journal of Neuroscience (2017), 37(16), 4243-4254

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 ... [more ▼]

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 neuro- modulation by neuroestrogens concerns the acute regulation of sensory coding by the auditory cortex as demonstrated by electrophys- iological studies of selected neurons in zebra finches. Yet, the spatial extent of such modulation by neuroestrogens is not known. Using functional magnetic resonance imaging, we demonstrate here that acute estrogen depletion alters within minutes auditory processing in male European starlings. These effects are confined to very specific but large areas of the auditory cortex. They are also specifically lateralized to the left hemisphere. Interestingly, the modulation of auditory responses by estrogens was much larger (both in amplitude and in topography) in March than in December or May/June. This effect was presumably independent from changes in circulating testosterone concentrations since levels of the steroid were controlled by subcutaneous implants, thus suggesting actions related to other aspects of the seasonal cycle or photoperiodic manipulations. Finally, we also show that estrogen production specifically modulates selectivity for behaviorally relevant vocalizations in a specific part of the caudomedial nidopallium. These findings confirm and extend previous conclusions that had been obtained by electrophysiological techniques. This approach provides a new very powerful tool to investigate auditory responsiveness in songbirds and its fast modulation by sex steroids. [less ▲]

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See detailTestosterone-induced neuroendocrine changes in the medial preoptic area precede song activation and plasticity in song control nuclei of female canaries
Shevchouk, Olesya ULiege; Ghorbanpoor, Samar; Ball, Gregory F et al

in European Journal of Neuroscience (2017), 45(7), 886-900

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 ... [more ▼]

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 testosterone action in POM increases sexually motivated singing. Here, we investigated the time course of testosterone action in the song control nuclei and POM, at the gross anatomical and cellular level. Photosensitive female canaries were injected with BrdU to label newborn neurons. One day later they were transferred to a long day photoperiod and implanted with testosterone-filled or empty implants. Brains and blood were collected 1, 2, 9 or 21 days later. Testosterone increased POM volume within one day, whereas the volume of song control nuclei increased significantly only on day 21 even if a trend was already observed for HVC on day 9. The density of newborn neurons in HVC, labeled by Bromodeoxyuridine (BrdU) and doublecortin, was increased by testosterone on days 9 and 21 although a trend was already detectable on day 2. In POM testosterone increased the number and size of aromatase-immunoreactive neurons already after one day. This rapid action of testosterone in POM supports its proposed role in controlling singing motivation. Although testosterone increased the number of newborn neurons in HVC rapidly (9, possibly 2 days), it is unlikely that these new neurons affect singing behavior before they mature and integrate into functional circuits. [less ▲]

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