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Biomedical subjects

Jacques Balthazart

Publications and source records attributed to Jacques Balthazart.

At least 19 recordsLinked to original sources
PubMed2007

Sex differences in projections from preoptic area aromatase cells to the periaqueductal gray in Japanese quail.

In many vertebrate species the medial preoptic area projects to a premotor nucleus, the periaqueductal central gray (PAG). This connection plays an important role in the control of reproductive behavior. In male Japanese quail (Coturnix japonica) specifically, the medial preoptic nucleus (POM), where various types of sensory inputs converge, is a critical site for the activational action of testosterone on male sexual behavior. To activate male copulatory behavior, testosterone must be aromatized to estradiol within the POM and aromatase-immunoreactive cells in the POM are the main source of projections to the PAG. The POM-PAG connection is thus an important functional circuit integrating the sensory with premotor components of sexual behavior. Contrary to what is observed in males, testosterone does not activate male-typical copulatory behavior in females and we investigated here via retrograde tracing methods whether this behavioral sexual difference is associated with a sex difference in connectivity between POM and PAG. Fluorescent microspheres were injected in the PAG of male and female quail and retrogradely labeled fluorescent cells counted in four fields of the POM in sections that had been immunolabeled for aromatase. Males had more aromatase-immunoreactive neurons projecting to the PAG than females and this difference was most prominent in the caudolateral part of the nucleus that has been specifically implicated in the control of male copulatory behavior. These data therefore support the hypothesis that sex differences in POM-PAG connectivity are causally linked to the sex difference in the behavioral response to testosterone.

Analysis of Variance↗
PubMed2006

Functional significance of the rapid regulation of brain estrogen action: where do the estrogens come from?

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

Afferent Pathways↗
PubMed2006

Social context affects testosterone-induced singing and the volume of song control nuclei in male canaries (Serinus canaria).

The contribution of social factors to seasonal plasticity in singing behavior and forebrain nuclei controlling song, and their interplay with gonadal steroid hormones are still poorly understood. In many songbird species, testosterone (T) enhances singing behavior but elevated plasma T concentrations are not absolutely required for singing to occur. Singing is generally produced either to defend a territory or to attract a mate and it is therefore not surprising that singing rate can be influenced by the sex and behavior of the social partner. We investigated, based on two independent experiments, the effect of the presence of a male or female partner on the rate of song produced by male canaries. In the first experiment, song rate was measured in dyads composed of one male and one female (M-F) or two males (M-M). Birds were implanted with T-filled Silastic capsules or with empty capsules as control. The number of complete song bouts produced by all males was recorded during 240 min on week 1, 2, 4, and 8 after implantation. On the day following each recording session, brains from approximately one-fourth of the birds were collected and the volumes of the song control nuclei HVC and RA were measured. T increased the singing rate and volume of HVC and RA but these effects were affected by the social context. Singing rates were higher in the M-M than in the M-F dyads. Also, in the M-M dyads a dominance-subordination relationship soon became established and dominant males sang at higher rates than subordinates in T-treated but not in control pairs. The differences in song production were not reflected in the size of the song control nuclei: HVC was larger in M-F than in M-M males and within the M-M dyads, no difference in HVC or RA size could be detected between dominant and subordinate males. At the individual level, the song rate with was positively correlated with RA and to a lower degree HVC volume, but this relationship was observed only in M-M dyads, specifically in dominant males. A second experiment, carried out with castrated males that were all treated with T and exposed either to another T-treated castrate or to an estradiol-implanted female, confirmed that song rate was higher in the M-M than in the M-F condition and that HVC volume was larger in heterosexual than in same-sex dyads. The effects of T on singing rate and on the volume of the song control nuclei are thus modulated by the social environment, including the presence/absence of a potential mate and dominance status among males.

Androgens↗
PubMed2006

Targeting steroid receptor coactivator-1 expression with locked nucleic acids antisense reveals different thresholds for the hormonal regulation of male sexual behavior in relation to aromatase activity and protein expression.

Steroid receptors such as the androgen and estrogen receptors require the presence of several proteins, known as coactivators, to enhance the transcription of target genes. The first goal of the present study was to define the role of SRC-1 on the steroid-dependent expression of the aromatase protein and its activity in male Japanese quail. The second goal was to analyze the rapid plasticity of the POM following antisense treatment interruption. We confirm here that the inhibition of SRC-1 expression by daily intracerebroventricular injections of locked nucleic acid antisense oligonucleotides in the third ventricle at the level of the preoptic area-hypothalamus (HPOA) significantly reduces testosterone-dependent male sexual behavior. In the first experiment, aromatase protein expression in HPOA was inhibited in SRC-1-depleted males but the enzymatic activity remained at the level measured in controls. We observed in the second experiment a recovery of the behavioral response to testosterone treatment after interruption of the antisense injection. However, several morphological characteristics of the POM were not different between the control group, the antisense-treated birds and antisense-treated birds in which treatment had been discontinued 3 days earlier. Antisense was also less effective in knocking-down SRC-1 in the present experiments as compared to our previous study. An analysis of this variation in the degree of knock-down of SRC-1 expression suggests dissociation among different aspects of steroid action on brain and behavior presumably resulting from the differential sensitivity of behavioral and neurochemical responses to the activation by testosterone and/or its estrogenic metabolites.

Analysis of Variance↗
PubMed2006

Is brain estradiol a hormone or a neurotransmitter?

Mounting evidence indicates that, besides their well-known hormonal mode of action at the genetic level, estrogens such as 17beta-estradiol also influence brain function by direct effects on neuronal membranes. Experimentally induced rapid changes in estradiol bioavailability in the brain have been shown to alter the expression of male sexual behavior significantly within minutes--probably too quickly to be accounted for by conventional genetic mechanisms. In parallel, recent studies indicate that aromatase, the enzyme that converts testosterone to estradiol in the brain, is expressed in presynaptic terminals and modulated within minutes by Ca(2+)-dependent phosphorylation. In this article, we develop the hypothesis that brain estrogens display many, if not all, functional characteristics of neuromodulators or even neurotransmitters.

Animals↗
PubMed2006

In vivo MR imaging of the seasonal volumetric and functional plasticity of song control nuclei in relation to song output in a female songbird.

In temperate zone songbird species, seasonal plasticity in the morphological and functional state of brain regions involved in song production occurs in association with seasonal changes in song output. Following MnCl(2)-injections in HVC (used as proper name) of female starlings, in vivo tract-tracing by Manganese Enhanced-Magnetic Resonance Imaging (ME-MRI) provided repeated measures of the volume of two HVC targets, the nucleus robustus arcopallii (RA) and area X, along with measures of the activity of the caudal motor pathway and rostral basal-ganglia pathway that control singing. Mn(2+)-labeling (volume labeled and signal intensity) of both nuclei was dramatically reduced in July (post-breeding season) when birds did not sing, compared to March (breeding season) when birds produced song. Seasonal changes in telencephalon volume did not exceed 4% and were not significant but were surprisingly correlated with individual measures of song rate and song bout length. Although individual song rates were variable in March, all MnCl(2)-injections led to a reliable labeling of area X and RA. In July, delineation of area X was only possible in two birds and RA could be delineated in 50% of the population; its volume had decreased by 46% as compared to March. The birds in which RA could be delineated in July had in March a higher activity of the HVC to area X projection as reflected by the total amount of Mn(2+) accumulated in area X, which suggests unexpected relationships between the two types of HVC projection neurons.

Animals↗
PubMed2006

Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens.

Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp(-/-)) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp(-/-) mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens.

Animals↗
PubMed2005

Socially induced and rapid increases in aggression are inversely related to brain aromatase activity in a sex-changing fish, Lythrypnus dalli.

Social interactions can generate rapid and dramatic changes in behaviour and neuroendocrine activity. We investigated the effects of a changing social environment on aggressive behaviour and brain aromatase activity (bAA) in a sex-changing fish, Lythrypnus dalli. Aromatase is responsible for the conversion of androgen into oestradiol. Male removal from a socially stable group resulted in rapid and dramatic (> or =200%) increases in aggression in the dominant female, which will become male usually 7-10 days later. These dominant females and recently sex-changed individuals had lower bAA but similar gonadal aromatase activity (gAA) compared to control females, while established males had lower bAA than all groups and lower gAA than all groups except dominant females. Within hours of male removal, dominant females' aggressive behaviour was inversely related to bAA but not gAA. These results are novel because they are the first to: (i) demonstrate socially induced decreases in bAA levels corresponding with increased aggression, (ii) identify this process as a possible neurochemical mechanism regulating the induction of behavioural, and subsequently gonadal, sex change and (iii) show differential regulation of bAA versus gAA resulting from social manipulations. Combined with other studies, this suggests that aromatase activity may modulate fast changes in vertebrate social behaviour.

Aggression↗
PubMed2005

Early seasonal development of brain song control nuclei in male blue tits.

In songbirds, the seasonal growth of the song system is generally thought to be controlled by the spring increase in plasma levels of testosterone and/or related changes in singing activity. Here we report an extremely early seasonal growth (before February) of the song control nuclei HVC and RA in Corsican blue tits (Parus caeruleus) indicating that the vernal development of these nuclei occurs well before the vernal increase in plasma testosterone, testes size and song activity. The development of HVC and RA occurred simultaneously in two populations that are known to breed consistently 1 month apart as an adaptation to heterogeneous landscapes (predominance of broad-leaved deciduous versus evergreen oak trees). The unidentified environmental and/or physiological cues controlling the plasticity in the song system must therefore differ, at least in part, from those affecting other morphological and physiological traits controlling reproduction.

Adaptation, Physiological↗
PubMed2005

Rapid control of brain aromatase activity by glutamatergic inputs.

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca2+ concentrations, such as the addition of glutamate agonists (kainate, alpha-amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-D-aspartate), but not of gamma-aminobutyric acid. The kainate effects, which reduce aromatase activity by 25-50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

Estradiol rapidly activates male sexual behavior and affects brain monoamine levels in the quail brain.

Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular effects mediated via non-genomic mechanisms have however been identified and one report showed that injections of estradiol rapidly stimulate chemoinvestigation and mounting behavior in castrated male rats. It is not known whether such effects take place in other species and what are the cellular underlying mechanisms. We show here that a single injection of estradiol (500 microg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone behaviorally ineffective by itself. The maximal behavioral effect was observed after 15 min. In a second experiment, the brain of all subjects was immediately collected after behavioral tests performed 15 min after injection. The preoptic area--hypothalamus (HPOA), hindbrain, telencephalon and cerebellum were isolated and monoamines measured by HPLC-ED. Estradiol increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/serotonin ratios in the telencephalon and hindbrain independently of whether animals had mated or not. Estradiol also affected these measures in HPOA and cerebellum but this effect was correlated with the level of sexual activity so that significant effects of the treatment only appeared when sexual activity was used as a covariate. Interactions between estradiol effects and sexual activity were also observed for dopamine in the HPOA and for serotonin in the hindbrain and cerebellum. Together, these data demonstrate that a single estradiol injection rapidly activates male sexual behavior in quail and that this behavioral effect is correlated with changes in monoaminergic activity.

Analysis of Variance↗
PubMed2005

Dopamine modulates male sexual behavior in Japanese quail in part via actions on noradrenergic receptors.

In rats, dopamine (DA) facilitates male sexual behavior through its combined action on D1- and D2-like receptors, in the medial preoptic area (MPOA) as well as other brain areas. In Japanese quail, systemic injections of dopaminergic drugs suggested a similar pharmacology but central injections have never been performed. Recent electrophysiological experiments demonstrated that DA effects in the MPOA of quail are mediated mainly through the activation of alpha2-noradrenergic receptors. Previous studies of DA action on behavior used specific dopaminergic agonists/antagonists and therefore unintentionally avoided the potential cross-reaction with alpha2-receptors. The present study was thus designed to investigate directly the effects of DA on male sexual behavior and to test whether the interaction of DA with heterologous receptors affects this behavior. Intracerebroventricular (i.c.v.) injection of DA or NE inhibited copulation in a dose-dependent manner. Systemic injections of yohimbine, an alpha2-noradrenergic antagonist, modulated copulation in a bimodal manner depending on the dose injected. Interestingly, a behaviorally ineffective dose of yohimbine markedly reduced the inhibitory effects of DA when injected 15min before. Together, these results show for the first time that i.c.v. injections of DA itself inhibit male sexual behavior in quail and suggest that the interaction of DA with alpha2-receptors has behavioral significance.

Adrenergic alpha-Antagonists↗
PubMed2005

Rapid effects of aromatase inhibition on male reproductive behaviors in Japanese quail.

Non-genomic effects of steroid hormones on cell physiology have been reported in the brain. However, relatively little is known about the behavioral significance of these actions. Male sexual behavior is activated by testosterone partly through its conversion to estradiol via the enzyme aromatase in the preoptic area (POA). Brain aromatase activity (AA) changes rapidly which might in turn be important for the rapid regulation of behavior. Here, acute effects of Vorozole, an aromatase inhibitor, injected IP at different doses and times before testing (between 15 and 60 min), were assessed on male sexual behavior in quail. To limit the risk of committing both types of statistical errors (I and II), data of all experiments were entered into a meta-analysis. Vorozole significantly inhibited mount attempts (P < 0.05, size effect [g] = 0.527) and increased the latency to first copulation (P < 0.05, g = 0.251). The treatment had no effect on the other measures of copulatory behavior. Vorozole also inhibited appetitive sexual behavior measured by the social proximity response (P < 0.05, g = 0.534) or rhythmic cloacal sphincter movements (P < 0.001, g = 0.408). Behavioral inhibitions always reached a maximum at 30 min. Another aromatase inhibitor, androstatrienedione, induced a similar rapid inhibition of sphincter movements. Radioenzyme assays demonstrated that within 30 min Vorozole had reached the POA and completely blocked AA measured in homogenates. When added to the extracellular milieu, Vorozole also blocked within 5 min the AA in POA explants maintained in vitro. Together, these data demonstrate that aromatase inhibition rapidly decreases both consummatory and appetitive aspects of male sexual behavior.

Animals↗
PubMed2005

Attraction thresholds and sex discrimination of urinary odorants in male and female aromatase knockout (ArKO) mice.

We previously found that both male and female aromatase knockout (ArKO) mice, which cannot synthesize estrogens due to a targeted mutation of the aromatase gene, showed less investigation of volatile body odors from anesthetized conspecifics of both sexes in Y-maze tests. We now ask whether ArKO mice are in fact capable of discriminating between and/or responding to volatile odors. Using habituation/dishabituation tests, we found that gonadectomized ArKO and wild-type (WT) mice of both sexes, which were tested without any sex hormone replacement, reliably distinguished between undiluted volatile urinary odors of either adult males or estrous females versus deionized water as well as between these two urinary odors themselves. However, ArKO mice of both sexes were less motivated than WT controls to investigate same-sex odors when they were presented last in the sequence of stimuli. In a second experiment, we compared the ability of ArKO and WT mice to respond to decreasing concentrations of either male or female urinary odors. We found a clear-cut sex difference in urinary odor attraction thresholds among WT mice: WT males failed to respond to urine dilutions higher than 1:20 by volume, whereas WT females continued to respond to urine dilutions up to 1:80. Male ArKO mice resembled WT females in their ability to respond to lower concentrations of urinary odors, raising the possibility that the observed sex difference among WT mice in urine attraction thresholds results from the perinatal actions of estrogen in the male nervous system. Female ArKO mice failed to show significant dishabituation responses to two (1:20 and 1:80) dilutions of female urine, perhaps, again, because of a reduced motivation to investigate less salient, same-sex urinary odors. Previously observed deficits in the preference of ArKO male and female mice to approach volatile body odors from conspecifics of either sex cannot be attributed to an inability of ArKO subjects to discriminate these odors according to sex but instead may reflect a deficient motivation to approach same-sex odors, especially when their concentration is low.

Animals↗
PubMed2005

Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit during a variety of listening tasks.

Auditory fMRI in humans has recently received increasing attention from cognitive neuroscientists as a tool to understand mental processing of learned acoustic sequences and analyzing speech recognition and development of musical skills. The present study introduces this tool in a well-documented animal model for vocal learning, the songbird, and provides fundamental insight in the main technical issues associated with auditory fMRI in these songbirds. Stimulation protocols with various listening tasks lead to appropriate activation of successive relays in the songbirds' auditory pathway. The elicited BOLD response is also region and stimulus specific, and its temporal aspects provide accurate measures of the changes in brain physiology induced by the acoustic stimuli. Extensive repetition of an identical stimulus does not lead to habituation of the response in the primary or secondary telencephalic auditory regions of anesthetized subjects. The BOLD signal intensity changes during a stimulation and subsequent rest period have a very specific time course which shows a remarkable resemblance to auditory evoked BOLD responses commonly observed in human subjects. This observation indicates that auditory fMRI in the songbird may establish a link between auditory related neuro-imaging studies done in humans and the large body of neuro-ethological research on song learning and neuro-plasticity performed in songbirds.

Acoustic Stimulation↗
PubMed2005

The effect of auditory distractors on song discrimination in male canaries (Serinus canaria).

Male songbirds such as canaries produce complex learned vocalizations that are used in the context of mate attraction and territory defense. Successful mate attraction or territorial defense requires that a bird be able to recognize individuals based on their vocal performance and identify these songs in a noisy background. In order to learn more about how birds are able to solve this problem, we investigated, with a two-alternative choice procedure, the ability of adult male canaries to discriminate between conspecific song segments from two different birds and to maintain this discrimination when conspecific songs are superimposed with a variety of distractors. The results indicate that male canaries have the ability to discriminate, with a high level of accuracy song segments produced by two different conspecific birds. Song discrimination was partially maintained when the stimuli were masked by auditory distractors, but the accuracy of the discrimination progressively declined as a function of the number of masking distractors. The type of distractor used in the experiments (other conspecific songs or different types of artificial white noise) did not markedly affect the rate of deterioration of the song discrimination. These data indicate that adult male canaries have the perceptual abilities to discriminate and selectively attend to one ongoing sound that occurs simultaneously with one or more other sounds. The administration of a noradrenergic neurotoxin did not impair markedly the discrimination learning abilities although the number of subjects tested was too small to allow any firm conclusion. In these conditions, however, the noradrenergic lesion significantly increased the number failures to respond in the discrimination learning task suggesting a role, in canaries, of the noradrenergic system in some attentional processes underlying song learning and processing.

Acoustic Stimulation↗
PubMed2005

Inhibition of steroid receptor coactivator-1 blocks estrogen and androgen action on male sex behavior and associated brain plasticity.

Studies of eukaryotic gene expression demonstrate the importance of nuclear steroid receptor coactivators in mediating efficient gene transcription. However, little is known about the physiological role of these coactivators in vivo. In Japanese quail, the steroid receptor coactivator-1 (SRC-1) is broadly expressed in steroid-sensitive brain areas that control the expression of male copulatory behavior, and we investigated the role of this coactivator by antisense technology. Daily intracerebroventricular injections of locked nucleic acid (LNA) antisense (AS) oligonucleotides targeting SRC-1 significantly reduced the expression of androgen- and estrogen-dependent male-typical sexual behaviors compared with control animals that received the vehicle alone or scrambled oligonucleotides. Sexual behavior was restored and even enhanced within 48 h after interruption of LNA injections. Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an overexpression 48 h after the end of injections. The effects of SRC-1 knock-down on behavior correlated with a reduction in volume of the preoptic medial nucleus (POM) when its borders were defined by Nissl staining or by aromatase immunohistochemistry. The amount of aromatase-immunoreactive material in POM was also reduced in the AS compared with the control group. Previous work on SRC-1 knock-out mice raised questions about the importance of this specific coactivator in the regulation of reproductive behavior and development of sexually dimorphic structures in the CNS. Together, the present findings indicate that SRC-1 modulates steroid-dependent gene transcription and behavior and highlight the rapid time course of steroid-induced brain plasticity in adult quail.

Androgen Antagonists↗