Biomedical subjects

Jacques Balthazart

Publications and source records attributed to Jacques Balthazart.

At least 37 records · Page 2Linked to original sources

PubMed2005

Endocrine correlates of the breeding asynchrony between two Corsican populations of blue tits (Parus caeruleus).

Analyses of the development of the reproductive system in seasonally breeding birds in the framework of long-term ecological studies are rare. Here, we present the first results of such a study in two Corsican populations of a European passerine bird, the blue tit (Parus caeruleus). The two study populations occupy different oak habitats and are separated by only 25 km. Despite their close proximity, they show a one-month difference in onset of egg laying, even after controlling for altitude. This micro-geographic difference in breeding date appears adaptive because both study populations raise chicks when food is most plentiful. In our study, males reached their maximum song activity during the egg-laying stage while maximal testosterone levels and testes sizes were reached 2-3 weeks before egg laying. The rate of development of the reproductive system in males was much faster in the earlier population, in spite of a similar onset of gonad development and song activity for the two study populations. No change in the volume of the song-control nuclei (HVC and RA) could be detected during the study period. Development of brain nuclei was completed 2-3 months before the beginning of intense sexual activity.

Animals↗

PubMed2005

Coordinated and dissociated effects of testosterone on singing behavior and song control nuclei in canaries (Serinus canaria).

Temperate zone songbirds that breed seasonally exhibit pronounced differences in reproductive behaviors including song inside and outside the breeding season. Springlike long daylengths are associated with increases in plasma testosterone (T) concentrations, as well as with increases in singing and in the volume of several brain nuclei known to control this behavior. The mechanisms whereby T can induce changes in behavior and brain, and whether or not these effects are differentially regulated, have recently begun to be examined, as has the question of the relative contributions of T and its androgenic and estrogenic metabolites to the regulation of this seasonal behavioral and neural plasticity. In this experiment, we examined the effects of T, 5alpha-dihydrotestosterone, or 17beta-estradiol treatment on castrated male canaries housed on short days and compared neural and behavioral effects in these males to similarly-housed males given only blank implants. We observed that only T treatment was effective in eliciting significant increases in singing behavior after 11 days of hormone exposure. In addition, T alone was effective in increasing the volume of a key song production nucleus, HVC. However, at this time, none of the steroids had any effects on the volumes of two other song control nuclei, Area X of the medial striatum and the robust nucleus of the arcopallium (RA), that are efferent targets of HVC, known to be regulated by androgen in canaries and also to play a role in the control of adult song. T can thus enhance singing well before concomitant androgen-induced changes in the song control system are complete.

Androgens↗

PubMed2005

Androgen mediation of conditioned rhythmic cloacal sphincter movements in Japanese Quail (Coturnix japonica).

Demonstrations of increased reproductive success due to sexual conditioning in Japanese quail (Coturnix japonica) have been reported, although the mechanisms that underlie these effects have remained elusive. One possible mechanism is conditioned rhythmic cloacal sphincter movements (RCSM). Two experiments were conducted with male quail to determine whether associations between a conditioned stimulus (CS) and a hen would result in the ability of the CS to elicit RCSM, and to explore the androgen mediation of conditioned RCSM. The results suggest that a focal CS paired with visual access to a female will elicit RCSM via a representation of the hen activated by the CS. Further, the available evidence indicates that conditioned RCSM is androgen mediated and that this learning may transfer across breeding seasons.

Anal Canal↗

PubMed2005

Modulation of hormonal signaling in the brain by steroid receptor coactivators.

Nuclear receptors, such as estrogen, glucocorticoid or thyroid hormone receptors, have been shown to play a critical role in brain development and physiology. The activity of these receptors is modulated by the interaction with several proteins and, in particular, coactivators are required to enhance their transcriptional activity. The steroid receptor coactivators (SRC-1, -2 and -3) are currently the best characterized coactivators and we review here the current knowledge on the distribution and function of these proteins in the brain. Knock-out models and antisense techniques have demonstrated the requirement for SRC-1 and -2 in the brain, focusing mainly on steroid and thyroid hormone-dependent development and behavior. The precise function of SRC-3 in the brain is currently unknown but its presence throughout the brain suggests an important function. Although the molecular biology of SRCs is relatively well known, the in vivo control of their expression, post-translational modifications and time- and cell-specific interactions with the different nuclear receptors remain elusive. A complete understanding of hormone action on brain and behavior will not be attained until a better knowledge of coactivator physiology is achieved.

Animals↗

PubMed2004

Electrophysiological and neurochemical characterization of neurons of the medial preoptic area in Japanese quail (Coturnix japonica).

Intracellular recordings of medial preoptic neurons demonstrated that most neurons show a spontaneous firing, a linear I-V relationship and low-threshold-like events suppressed by the application of Ni2+. Some neurons had a depolarizing sag of the membrane potential in response to hyperpolarizing current pulses. The majority of the cells exhibited a robust spontaneous synaptic activity suppressed by SR95531 (100 microM), a GABAA receptor antagonist, and/or by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate (KA) glutamate receptor antagonist. Most neurons were affected by the application of AMPA (10 microM), kainate (30 microM), N-methyl-D-aspartic acid (NMDA, 10 microM), isoguvacine (a GABAA receptor agonist, 100 microM), dopamine (100 microM), and norepinephrine (100 microM). Biocytin injections coupled to aromatase immunocytochemistry identified 19 recorded neurons including 3 displaying a dense aromatase immunoreactivity. All of them responded to kainate, dopamine, and norepinephrine, while only one responded to isoguvacine and NMDA. Taken together, these results demonstrate a relative electrical and neurochemical homogeneity of the medial preoptic neurons, including a few aromatase-immunoreactive neurons that could be identified by immunocytochemistry after biocytin labeling of the recorded neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2004

Hormonal regulation of brain circuits mediating male sexual behavior in birds.

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior, because their behavior can be studied in the context of a large amount of field data, well-defined neural circuits related to reproductive behavior have been described, and the avian neuroendocrine system exhibits many examples of marked plasticity. As is the case in other taxa, male sexual behavior in birds can be usefully divided into an appetitive phase consisting of variable behaviors (typically searching and courtship) that allow an individual to converge on a functional outcome, copulation (consummatory phase). Based primarily on experimental studies in ring doves and Japanese quail, it has been shown that testosterone of gonadal origin plays an important role in the activation of both of these aspects of male sexual behavior. Furthermore, the conversion of androgens, such as testosterone, in the brain to estrogens, such as 17beta-estradiol, is essential for the full expression of male-typical behaviors. The localization of sex steroid receptors and the enzyme aromatase in the brain, along with lesion, hormone implant and immediate early gene expression studies, has identified many neural sites related to the control of male behavior. The preoptic area (POA) is a key site for the integration of sensory inputs and the initiation of motor outputs. Furthermore, prominent connections between the POA and the periaqueductal gray (PAG) form a node that is regulated by steroid hormones, receive sensory inputs and send efferent projections to the brainstem and spinal cord that activate male sexual behaviors. The sensory inputs regulating avian male sexual responses, in contrast to most mammalian species, are primarily visual and auditory, so a future challenge will be to identify how these senses impinge on the POA-PAG circuit. Similarly, most avian species do not have an intromittent organ, so the projections from the POA-PAG to the brainstem and spinal cord that control sexual reflexes will be of particular interest to contrast with the well characterized rodent system. With this knowledge, general principles about the organization of male sexual circuits can be elucidated, and comparative studies relating known species variation in avian male sexual behaviors to variation in neural systems can be pursued.

Androgens↗

PubMed2004

Preoptic aromatase modulates male sexual behavior: slow and fast mechanisms of action.

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by testosterone aromatization. Estrogens bind to intracellular receptors, which then act as transcription factors to activate the behavior. Accordingly, changes in aromatase activity (AA) result from slow steroid-induced modifications of enzyme transcription. More recently, rapid nongenomic effects of estrogens have been described and evidence has accumulated indicating that AA can be modulated by rapid (minutes to hour) nongenomic mechanisms in addition to the slower transcriptional changes. Hypothalamic AA is rapidly down-regulated in conditions that enhance protein phosphorylation, in particular, increases in the intracellular calcium concentration, such as those triggered by neurotransmitter (e.g., glutamate) activity. Fast changes in brain estrogens can thus be caused by aromatase phosphorylation as a result of changes in neurotransmission. In parallel, recent studies demonstrate that the pharmacological blockade of AA by specific inhibitors rapidly (within 15-45 min) down-regulates motivational and consummatory aspects of male sexual behavior in quail while injections of estradiol can rapidly increase the expression of copulatory behavior. These data collectively support an emerging concept in neuroendocrinology, namely that estrogen, locally produced in the brain, regulates male sexual behavior via a combination of genomic and nongenomic mechanisms. Rapid and slower changes of brain AA match well with these two modes of estrogen action and provide temporal variations in the estrogen's bioavailability that can support the entire range of established effects for this steroid.

Animals↗

PubMed2004

The effects of aromatase inhibition on testosterone-dependent conditioned rhythmic cloacal sphincter movements in male Japanese quail.

Male Japanese quail produce a foam that, along with semen, is transferred to the quail hen during copulation. This foam has been reported to increase fertility, prolong sperm motility, and enhance sperm competition. Action of the cloacal sphincter muscles in response to visual exposure to a female produces the foam. The rhythmic cloacal sphincter movements (RCSM) responsible for foam production in male quail is elicited by a conditioned stimulus (CS) previously paired with access to a quail hen. These conditioned RCSM are testosterone-dependent. The present experiment was conducted to explore whether, as is the case with most other testosterone-dependent male sexual behaviors in the quail, conditioned RCSM are mediated by the aromatization of testosterone. Castrated, testosterone-treated male quail were presented with paired presentations of an arbitrary focal CS and visual access to a female. Once conditioned RCSM had developed, subjects received twice daily injections of the aromatase inhibitor Vorozole (R083842) during a series of extinction test presentations of the CS. Injections of Vorozole significantly decreased the number of RCSMs elicited by a sexual CS. This decrease was specific to sexual RCSM; cloacal sphincter movements that occurred following defecation were not affected by Vorozole. Conditioned sexual RCSM are therefore mediated by the aromatization of testosterone, most likely due to effects on central aromatase activity related to sexual motivation.

Animals↗

PubMed2004

Rapid regulation of pain by estrogens synthesized in spinal dorsal horn neurons.

In addition to exerting genomic actions via nuclear receptors within hours to days, estrogens also regulate neuronal activity much faster (within seconds) by activating neuronal membrane receptors coupled to intracellular second-messenger pathways. To date, the origin of estrogens inducing rapid effects in the brain remains unclear, although it is often ascribed to the gonads. We report here that an acute blockade of the endogenous synthesis of estrogens in the quail spinal dorsal horn markedly reduced, within 1 min, the behavioral responsiveness to a thermal painful stimulus. Similar rapid effects in the opposite direction were induced by estradiol. This finding identifies a new paracrine and nongenomic mechanism for the regulation of pain by estrogens. Such regulation was assumed previously to result only from slow genomic actions of estrogens arising from the ovaries. Also, quite importantly, this finding suggests that the numerous rapid nongenomic effects of estrogens in the CNS could depend on their immediate local production by the enzyme aromatase, independently from the gonads.

Animals↗

PubMed2004

Catecholaminergic inputs to aromatase cells in the canary auditory forebrain.

The caudomedial nidopallium in songbirds is a specialized forebrain auditory region involved in the processing of species-typical vocalizations. It receives a prominent catecholaminergic projection with many fibers forming basket-like structures around non-immunoreactive cells. We investigated in male canaries the anatomical relationship between tyrosine hydroxylase and cells immunoreactive for the steroid metabolizing enzyme, aromatase, in the caudomedial nidopallium using double-label immunocytochemistry. Fibers immunoreactive for tyrosine hydroxylase established numerous close contacts with aromatase-immunoreactive cells and often encircled these cells to form basket-like structures. Aromatase containing cells in the caudomedial nidopallium are therefore a major target of catecholaminergic inputs in canary. Interactions between catecholaminergic systems and aromatase in the caudomedial nidopallium may provide one mechanism for the regulation of estrogens involved in song perception and memorization.

Animals↗

PubMed2004

Immunocytochemical localization of aromatase in sensory and integrating nuclei of the hindbrain in Japanese quail (Coturnix japonica).

The distribution of the estrogen synthesizing enzyme (aromatase) in the hindbrain (rhombencephalon and mesencephalon) of male adult quail was investigated by immunocytochemistry. Aromatase-immunoreactive neuronal structures (perikarya and fibers bearing punctate structures) were observed in sensory (trigeminal, solitary tract, vestibular, optic tectum) and integrating (parabrachial, periaqueductal, cerulean, raphe) nuclei. Besides the expression of aromatase in these well-delineated nuclei, dense to scattered networks of immunoreactive fibers were found dispersed throughout the hindbrain and, in particular, in its rostral and dorsal parts. To a lesser extent, they were also present throughout the premotor nuclei of the reticular formation and in various fiber tracts. In contrast, no immunoreactive signal was found in motor nuclei, and in most of the statoacoustic (cerebellum, cochlear, olive, pontine, part of vestibular) nuclei. The expression of aromatase in perikarya and fibers in areas of the adult hindbrain where estrogen receptors have been identified previously suggests a role for estrogens locally produced in the regulation of sensory and integrating functions, contrary to the widespread assumption that these functions are regulated exclusively by steroids produced in the gonads.

Animals↗

PubMed2004

Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds.

The song control system of song birds is an excellent model for studying brain plasticity and has thus far been extensively analyzed by histological and electrophysiological methods. However, these approaches do not provide a global view of the brain and/or do not allow repeated measures, which are necessary to establish correlations between alterations in neural substrate and behavior. Application of in vivo manganese-enhanced MRI enabled us for the first time to visualize the song control system repeatedly in the same bird, making it possible to quantify dynamically the volume changes in this circuit as a function of seasonal and hormonal influences. In this review, we introduce and explore the song control system of song birds as a natural model for brain plasticity to validate a new cutting edge technique, which we called 'repeated dynamic manganese enhanced MRI' or D-MEMRI. This technique is based on the use of implanted permanent cannulae--for accurate repeated manganese injections in a defined target area--and the subsequent MRI acquisition of the dynamics of the accumulation of manganese in projection brain targets. A compilation of the D-MEMRI data obtained thus far in this system demonstrates the usefulness of this new method for studying brain plasticity. In particular it is shown to be a perfect tool for long-term studies of morphological and functional responses of specific brain circuits to changes in endocrine conditions. The method was also successfully applied to obtain quantitative measures of changes in activity as a function of auditory stimuli in different neuronal populations of a same nucleus that project to different targets. D-MEMRI, combined with other MRI techniques, clearly harbors potential for unraveling seasonal, hormonal, pharmacological or even genetically driven changes in a neuronal circuit, by simultaneously measuring changes in morphology, activity and connectivity.

Adaptation, Physiological↗

PubMed2004

Differential effects of testosterone on neuronal populations and their connections in a sensorimotor brain nucleus controlling song production in songbirds: a manganese enhanced-magnetic resonance imaging study.

Nucleus HVC (formerly called high vocal center) of songbirds contains two types of projecting neurons connecting HVC respectively to the nucleus robustus archistriatalis, RA, or to area X. These two neuron classes exhibit multiple neurochemical differences and are differentially replaced by new neurons during adult life: high rates of neuronal replacement are observed in RA-projecting neurons only. The activity of these two types of neurons may also be modulated differentially by steroids. We analyzed by magnetic resonance imaging the effect of testosterone on the volume of RA and area X and on the dynamics of Mn(2+) accumulation in RA and area X of female starlings that had been injected with MnCl(2) through a permanent cannula implanted in HVC. Repeated visualization 6 weeks apart (before and after testosterone treatment) identified a volume increase of both nuclei in testosterone-treated birds associated with a concomitant decrease in controls. Following testosterone treatment, the total amount of Mn(2+) transported to RA and area X increased but the dynamics of accumulation, reflecting in part the activity of HVC neurons, was specifically altered in area X but not in RA. These data indicate that testosterone differentially affects the RA- and area X-projecting neurons in HVC. Manganese-enhanced magnetic resonance imaging (ME-MRI) thus provides repeated measures of connected brain areas and demonstrates testosterone-dependent regionally specific changes in brain activity and functional connectivity. The slow time scales investigated by this technique (compared to functional MRI) appear ideally suited for characterizing slow processes such as those involved in brain plasticity and learning.

Animals↗

PubMed2004

Territorial aggression, circulating levels of testosterone, and brain aromatase activity in free-living pied flycatchers.

Testosterone (T) is a critical endocrine factor for the activation of many aspects of reproductive behavior in vertebrates. Castration completely eliminates the display of aggressive and sexual behaviors that are restored to intact level by a treatment with exogenous T. There is usually a tight correlation between the temporal changes in plasma T and the frequency of reproductive behaviors during the annual cycle. In contrast, individual levels of behavioral activity are often not related to plasma T concentration at the peak of the reproductive season suggesting that T is available in quantities larger than necessary to activate behavior and that other factors limit the expression of behavior. There is some indication from work in rodents that individual levels of brain aromatase activity (AA) may be a key factor that limits the expression of aggressive behavior, and in agreement with this idea, many studies indicate that estrogens produced in the brain by the aromatization of T may contribute to the activation of reproductive behavior, including aggression. We investigated here in pied flycatcher (Ficedula hypoleuca) the relationships among territorial aggression, plasma T, and brain AA at the peak of the reproductive season. In a first experiment, blood samples were collected from unpaired males holding a primary territory and, 1 or 2 days later, their aggressive behavior was quantified during standardized simulated territorial intrusions. No relationship was found between individual differences in aggressive behavior and plasma T or dihydrotestosterone levels but a significant negative correlation was observed between number of attacks and plasma corticosterone. In a second experiment, aggressive behavior was measured during a simulated territorial intrusion in 22 unpaired males holding primary territories. They were then immediately captured and AA was measured in their anterior and posterior diencephalon and in the entire telencephalon. Five males that had attracted a female (who had started egg-laying) were also studied. The paired males were less aggressive and correlatively had a lower AA in the anterior diencephalon but not in the posterior diencephalon and telencephalon than the 22 birds holding a territory before arrival of a female. In these 22 birds, a significant correlation was observed between number of attacks/min displayed during the simulated territorial intrusion and AA in the anterior diencephalon but no correlation was found between these variables in the two other brain areas. Taken together, these data indicate that the level of aggression displayed by males defending their primary territory may be limited by the activity of the preoptic aromatase, but plasma T is not playing an important role in establishing individual differences in aggression. Alternatively, it is also possible that brain AA is rapidly affected by agonistic interactions and additional work should be carried out to determine whether the correlation observed between brain AA and aggressive behavior is the result of an effect of the enzyme on behavior or vice versa. In any case, the present data show that preoptic AA can change quite rapidly during the reproductive cycle (within a few days after arrival of the female) indicating that this enzymatic activity is able to regulate rapid behavioral transitions during the reproductive cycle in this species.

Aggression↗

PubMed2004

Seasonal plasticity in the song control system: multiple brain sites of steroid hormone action and the importance of variation in song behavior.

Birdsong, in non-tropical species, is generally more common in spring and summer when males sing to attract mates and/or defend territories. Changes in the volumes of song control nuclei, such as HVC and the robust nucleus of the arcopallium (RA), are observed seasonally. Long photoperiods in spring stimulate the recrudescence of the testes and the release of testosterone. Androgen receptors, and at times estrogen receptors, are present in HVC and RA as are co-factors that facilitate the transcriptional activity of these receptors. Thus testosterone can act directly to induce changes in nucleus volume. However, dissociations have been identified at times among long photoperiods, maximal concentrations of testosterone, large song control nuclei, and high rates of song. One explanation of these dissociations is that song behavior itself can influence neural plasticity in the song system. Testosterone can act via brain-derived neurotrophic factor (BDNF) that is also released in HVC as a result of song activity. Testosterone could enhance song nucleus volume indirectly by acting in the preoptic area, a region regulating sexual behaviors, including song, that connects to the song system through catecholaminergic cells. Seasonal neuroplasticity in the song system involves an interplay among seasonal state, testosterone action, and behavioral activity.

Animals↗

PubMed2003

Specific innervation of aromatase neurons by substance P fibers in the dorsal horn of the spinal cord in quail.

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein.

Androgens↗

PubMed2003

Effect of age and testosterone on autumnal neurogenesis in male European starlings (Sturnus vulgaris).

The male European starling (Sturnus vulgaris) is an open-ended learner that increases its repertoire throughout life. In parallel, the volume of high vocal center (HVC) is larger in older birds than in yearlings. We labeled with the thymidine analog 5'-bromodeoxyuridine (BrdU) the cells that are generated during the fall in the brain of adult males that were 2 or more years old and in yearling males that were treated with exogenous testosterone (T) or kept intact before BrdU administration. In all subjects, the singing rate was recorded and BrdU-labeled cells were quantified in HVC, in proliferative areas of the ventricular zone (VZ) and in auditory regions. BrdU-containing cells were observed in all brain regions investigated. They were significantly more numerous in the VZ of the T-treated yearlings than in any other group. In older birds, a reduced number of labeled cells was specifically observed in the VZ close to the anterior commissure. No group difference was detected in auditory processing areas or in HVC. These data show for the first time a positive influence of T on the production of new cells at the VZ level in a male songbird and a decrease of this process with age. Furthermore, in T-treated birds, a correlation was observed between the HVC volume and the number of differentiated (round) BrdU-positive cell numbers in HVC on the one hand and song rate on another hand supporting the notion that singing activity is causally related to the T-induced growth of this song control nucleus.

Aging↗

PubMed2003

Effects of testosterone on Reelin expression in the brain of male European starlings.

Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. We studied the expression of Reelin in the brain of adult male European starlings that had been treated or not with exogenous testosterone. Reelin-immunoreactive cells and fibers were widely distributed in the forebrain including areas in and around the song control nucleus, HVC. No labeling was detected in other song control nuclei with the exception of nucleus uvaeformis, which was delineated by a dense cluster of Reelin-immunoreactive perikarya. Reelin is thus expressed in areas incorporating new neurons in adulthood, such as HVC. Reelin expression was sharply decreased by testosterone in HVC, nucleus uvaeformis and dorsal thalamus but not in other brain regions. These results are consistent with the idea that seasonal changes in Reelin expression modulate the incorporation of neurons within HVC. The presence of Reelin in other brain areas that do not incorporate new neurons in adulthood indicates, however, that this protein must play other unrelated roles in the adult brain. Additional studies should now be carried out to determine the specific role played by this protein in the seasonal plasticity of the songbird brain.

Animals↗