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Barney A. Schlinger - One of the best experts on this subject based on the ideXlab platform.
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Determinants and significance of corticosterone regulation in the Songbird brain
General and comparative endocrinology, 2015Co-Authors: Michelle A. Rensel, Barney A. SchlingerAbstract:Abstract Songbirds exhibit significant adult neuroplasticity that, together with other neural specializations, makes them an important model system for neurobiological studies. A large body of work also points to the Songbird brain as a significant target of steroid hormones, including corticosterone (CORT), the primary avian glucocorticoid. Whereas CORT positively signals the brain for many functions, excess CORT may interfere with natural neuroplasticity. Consequently, mechanisms may exist to locally regulate CORT levels in brain to ensure optimal concentrations. However, most studies in Songbirds measure plasma CORT as a proxy for levels at target tissues. In this paper, we review literature concerning circulating CORT and its effects on behavior in Songbirds, and discuss recent work suggesting that brain CORT levels are regulated independently of changes in adrenal secretion. We review possible mechanisms for CORT regulation in the avian brain, including corticosteroid-binding globulins, p-glycoprotein activity in the blood–brain barrier and CORT metabolism by the 11s hydroxysteroid dehydrogenases. Data supporting a role for CORT regulation within the Songbird brain have only recently begun to emerge, suggesting that this is an avenue for important future research.
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Neurosteroidogenesis: Insights from Studies of Songbirds
Journal of neuroendocrinology, 2011Co-Authors: Barney A. Schlinger, Luke Remage-healeyAbstract:The long-held dogma that the brain is a target of steroids produced by peripheral organs has delayed the widespread acceptance of the functional importance of neurosteroidogenesis. Comparative studies have been vital for establishing the key actions of gonadal and adrenal hormones on brain and behaviour. No doubt, studies across diverse phyla will continue to be crucial for revealing the true significance of neurosteroidogenesis to proper function of the vertebrate brain. Here, we review work carried out in our laboratory, as well as in others, highlighting advances to our understanding of brain steroid synthesis and action using Songbirds as animal models. These studies show that steroidogenic transporters and enzymes are present in the Songbird brain and that their expression and/or activities are subject to developmental, seasonal or short-term regulation. Our work in a Songbird points to synaptic synthesis of neuroactive steroids and fast, perisynaptic membrane actions. Combined with evidence for rapid steroidal control of behaviour, these studies firmly establish a neuromodulatory role for avian neurosteroids. We hope this work will join with that of other species to embolden the acceptance of neurosteroidal signalling as a core property of vertebrate neurobiology.
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Recovery of motor and cognitive function after cerebellar lesions in a Songbird – role of estrogens
The European journal of neuroscience, 2009Co-Authors: Rory D. Spence, Stephanie A. White, Barney A. Schlinger, Yin Zhen, Lainy B. DayAbstract:In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Songbirds are particularly good models for the investigation of motor and cognitive processes but little is known about the role of the Songbird cerebellum in these processes. To explore cerebellar function in a Songbird, we lesioned the cerebellum of adult female zebra finches and examined the effects on a spatial working memory task and on motor function during this task. There is evidence for steroid synthesis in the Songbird brain and neurosteroids may have an impact on some forms of neural plasticity in adult Songbirds. We therefore hypothesized that neurosteroids would affect motor and cognitive function after a cerebellar injury. We found that cerebellar lesions produced deficits in motor and cognitive aspects of a spatial task. In line with our prediction, birds in which estrogen synthesis was blocked had impaired performance in our spatial task compared with those that had estrogen synthesis blocked but estrogen replaced. There was no clear effect of estrogen replacement on motor function. We also found that lesions induced expression of the estrogen synthetic enzyme aromatase in reactive astrocytes and Bergmann glia around a cerebellar lesion. These data suggest that the cerebellum of Songbirds mediates both motor and cognitive function and that estrogens may improve the recovery of cognitive aspects of cerebellar function after injury.
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Steroidogenesis and Neuroplasticity in the Songbird Brain
Neuroactive Steroids in Brain Function Behavior and Neuropsychiatric Disorders, 2008Co-Authors: Colin J. Saldanha, Barney A. SchlingerAbstract:The vertebrate brain is a source and target of steroid hormones. Songbirds have long provided an array of structural and behavioral endpoints towards understanding how steroid molecules affect neuroanatomy and neurophysiology. More recently, our conceptualization of the brain has expanded to include the CNS as a potent source of these very steroids. Here we review recent findings about the expression of steroidogenic enzymes in the Songbird brain with particular emphasis upon the role of neurosteroidogenesis on the plasticity of brain circuits. We include examples of natural neuroplasticity in laboratory and field studies. Additionally, we discuss the role of neurosteroidogenesis on the outcomes of pathological brain damage. These two areas of research have provided novel and fundamentally restructured hypotheses as to the role of neurosteroidogenesis in brain function. Notable among recent findings from such studies, are the consideration of alternate substrates for steroidogenic enzymes, an expansion of the suite of enzymes found at sites of neuronal recruitment and the expression of these enzymes in additional cell types and ultrastructural compartments. The powerful link among ethology, physiology, anatomy and cell biology is exemplified in these vertebrates and renders the Songbird an enduring model for the study of the role of de novo steroid synthesis on the plasticity of brain structure and function.
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3beta-HSD activates DHEA in the Songbird brain.
Neurochemistry international, 2007Co-Authors: Barney A. Schlinger, Devaleena S Pradhan, Kiran K SomaAbstract:Dehydroepiandrosterone (DHEA) is an abundant circulating prohormone in humans, with a variety of reported actions on central and peripheral tissues. Despite its abundance, the functions of DHEA are relatively unknown because common animal models (laboratory rats and mice) have very low DHEA levels in the blood. Over the past decade, we have obtained considerable evidence from avian studies demonstrating that (1) DHEA is an important circulating prohormone in Songbirds and (2) the enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD), responsible for converting DHEA into a more active androgen, is expressed at high levels in the Songbird brain. Here, we first review biochemical and molecular studies demonstrating the widespread activity and expression of 3beta-HSD in the adult and developing Songbird brain. Studies examining neural 3beta-HSD activity show effects of sex, stress, and season that are region-specific. Second, we review studies showing seasonal and stress-related changes in circulating DHEA in captive and wild Songbird species. Third, we describe evidence that DHEA treatment can stimulate song behavior and the growth of neural circuits controlling song behavior. Importantly, brain 3beta-HSD and aromatase can work in concert to locally metabolize DHEA into active androgens and estrogens, which are critical for controlling behavior and robust adult neuroplasticity in Songbirds. DHEA is likely secreted by the avian gonads and/or adrenals, as is the case in humans, but DHEA may also be synthesized de novo in the Songbird brain from cholesterol or other precursors. Irrespective of its source, DHEA seems to be an important prohormone in Songbirds, and 3beta-HSD is a key enzyme in the Songbird brain.
Gregory F Ball - One of the best experts on this subject based on the ideXlab platform.
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the Songbird neurogenomics song initiative community based tools and strategies for study of brain gene function and evolution
BMC Genomics, 2008Co-Authors: Kirstin Replogle, Gregory F Ball, Arthur P Arnold, Mark Band, Staffan Bensch, Eliot A Brenowitz, Shu Dong, Jenny Drnevich, Margaret Ferris, J GeorgeAbstract:Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse Songbird species and natural contexts. We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500–15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other Songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the Songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. Immediately, these results set the foundation for a coordinated set of 25 planned experiments by 16 research groups probing fundamental links between genome, brain, evolution and behavior in Songbirds. Energetic application of genomic resources to research using Songbirds should help illuminate how complex neural and behavioral traits emerge and evolve.
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Comparative studies of sex differences in the song-control system of Songbirds
Trends in neurosciences, 1999Co-Authors: Scott A. Macdougall-shackleton, Gregory F BallAbstract:Songbirds exhibit some of the most extreme sex differences in the brain of all vertebrates. Understanding the function of these sex differences has relied on making interspecies comparisons. In some species, females sing rarely or not at all, and the brain nuclei that control song are many times larger in volume in males than in females. In other species, males and females sing approximately equally, and the sizes of the brain nuclei that control song are approximately equal between the sexes. This article reviews sex differences in the song-control system of Songbirds, and introduces statistical comparative methods developed by evolutionary biologists. These methods control for phylogenetic effects while comparing the co-evolution of traits. The extreme sex differences in song seem to have co-evolved with the extreme sex differences in singing behavior in Songbird species.
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Neurochemical Specializations Associated with Vocal Learning and Production in Songbirds and Budgerigars
Brain behavior and evolution, 1994Co-Authors: Gregory F BallAbstract:Specialized neural circuitry has evolved in groups of birds where vocal learning is known to occur, such as in the oscine suborder of the Passeriformes (song-birds) and in the order Psittaciformes (parrots). These specializations are most prominent in the telencephalon, while the midbrain and medullary portions of the vocal control circuit are generally similar in all orders of birds. Specializations in Songbirds have at least four components: 1) a set of distinct and interconnected vocal control nuclei in the forebrain; 2) unique connections between the auditory system and these vocal control nuclei; 3) the occurrence of receptors for sex steroid hormones in a subset of the vocal control nuclei; and 4) unique patterns in the distribution of various markers of the major classes of neurotransmitters within the vocal control nuclei. In the order Psittaciformes, as exemplified by budgerigars (Melopsittacus undulatus), it appears that neural specializations generally similar to those described in Songbirds have evolved independently. Although anatomical studies have found a system of interconnected forebrain regions in budgerigars that are roughly similar to those described in oscines, detailed connectivity studies of this forebrain system suggest that it is only superficially similar to that of Songbirds, and budgerigars also have unique connections between the auditory and motor systems. Also, analyses of the distribution of markers of neurotransmitter function in the budgerigar brain reveal patterns different from those described in Songbird vocal control systems. This work suggests that Songbirds and parrots have evolved separate neural ‘solutions’ to solve the problem of vocal plasticity. There are differences between these 'solutions' but also similarities that may be the result of convergent evolution. Although vocal behavior is learned in both Songbirds and parrots, it differs in many respects. By taking advantage of this 'natural' experiment one can gain insight into the hormonal and neural events that mediate these different forms of vocal plasticity.
Lynn Thompson - One of the best experts on this subject based on the ideXlab platform.
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Androgen Synthesis in a Songbird: A Study of Cyp17 (17α-Hydroxylase/C17,20-Lyase) Activity in the Zebra Finch
General and Comparative Endocrinology, 1999Co-Authors: Barney A. Schlinger, Nathaniel Ira Lane, William Grisham, Lynn ThompsonAbstract:Abstract Androgens and estrogens influence the maturation and function of numerous tissues in both male and female birds, especially the brains of the oscine Songbirds. Although there exist a very large number of studies that have investigated circulating sex steroids in many species of wild and captive-held Songbirds, there remain a significant number of questions about the sites of synthesis of the active steroids that act on the Songbird brain. Estrogens are derived from androgen. Thus, the synthesis of androgen itself is critical for both androgen- and estrogen-dependent actions in both male and female Songbirds. Therefore, we have undertaken studies of the enzyme 17α-hydroxylase/C17,20-lyase (Cyp17), the enzyme responsible for the synthesis of androgens from their progestin or pregnane precursors via their 17α-hydroxy intermediates. Here we have characterized optimal conditions for measuring Cyp17 in gonads of adult zebra finches via the conversion of tritiated [ 3 H]progesterone into 17α-hydroxy P (17α-hydroxylase activity) and androstenedione and testosterone (C17,20-lyase) activity. Cyp17 activity is abundant in testis, with lesser amounts in ovary. Low levels of Cyp17 activity were also detected in male adrenals, but not in any other tissue, including brain. Testicular Cyp17 activity is readily inhibited in vitro by ketoconazole, a specific Cyp17 inhibitor. Ketoconazole works less well in vivo. In males castrated and/or treated with fadrozole, an inhibitor of aromatase, we detected no extragonadal sites of Cyp17 activity, although fadrozole appeared to increase circulating androgens in both castrated and intact males. Thus, we still do not know the site of androgen synthesis in these males. Further studies of Cyp17 will be useful in understanding more about the mechanisms of androgen delivery to neural circuits in adult and developing Songbirds.
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androgen synthesis in a Songbird a study of cyp17 17α hydroxylase c17 20 lyase activity in the zebra finch
General and Comparative Endocrinology, 1999Co-Authors: Barney A. Schlinger, Nathaniel Ira Lane, William Grisham, Lynn ThompsonAbstract:Abstract Androgens and estrogens influence the maturation and function of numerous tissues in both male and female birds, especially the brains of the oscine Songbirds. Although there exist a very large number of studies that have investigated circulating sex steroids in many species of wild and captive-held Songbirds, there remain a significant number of questions about the sites of synthesis of the active steroids that act on the Songbird brain. Estrogens are derived from androgen. Thus, the synthesis of androgen itself is critical for both androgen- and estrogen-dependent actions in both male and female Songbirds. Therefore, we have undertaken studies of the enzyme 17α-hydroxylase/C17,20-lyase (Cyp17), the enzyme responsible for the synthesis of androgens from their progestin or pregnane precursors via their 17α-hydroxy intermediates. Here we have characterized optimal conditions for measuring Cyp17 in gonads of adult zebra finches via the conversion of tritiated [ 3 H]progesterone into 17α-hydroxy P (17α-hydroxylase activity) and androstenedione and testosterone (C17,20-lyase) activity. Cyp17 activity is abundant in testis, with lesser amounts in ovary. Low levels of Cyp17 activity were also detected in male adrenals, but not in any other tissue, including brain. Testicular Cyp17 activity is readily inhibited in vitro by ketoconazole, a specific Cyp17 inhibitor. Ketoconazole works less well in vivo. In males castrated and/or treated with fadrozole, an inhibitor of aromatase, we detected no extragonadal sites of Cyp17 activity, although fadrozole appeared to increase circulating androgens in both castrated and intact males. Thus, we still do not know the site of androgen synthesis in these males. Further studies of Cyp17 will be useful in understanding more about the mechanisms of androgen delivery to neural circuits in adult and developing Songbirds.
Manfred Gahr - One of the best experts on this subject based on the ideXlab platform.
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Video_1_Tissue Clearing and Light Sheet Microscopy: Imaging the Unsectioned Adult Zebra Finch Brain at Cellular Resolution.MP4
2019Co-Authors: Mariana Diales Rocha, Daniel Normen Düring, Philipp Bethge, Fabian F. Voigt, Staffan Hildebrand, Fritjof Helmchen, Alexander Pfeifer, Richard Hans Robert Hahnloser, Manfred GahrAbstract:The inherent complexity of brain tissue, with brain cells intertwining locally and projecting to distant regions, has made three-dimensional visualization of intact brains a highly desirable but challenging task in neuroscience. The natural opaqueness of tissue has traditionally limited researchers to techniques short of single cell resolution such as computer tomography or magnetic resonance imaging. By contrast, techniques with single-cell resolution required mechanical slicing into thin sections, which entails tissue distortions that severely hinder accurate reconstruction of large volumes. Recent developments in tissue clearing and light sheet microscopy have made it possible to investigate large volumes at micrometer resolution. The value of tissue clearing has been shown in a variety of tissue types and animal models. However, its potential for examining the Songbird brain remains unexplored. Songbirds are an established model system for the study of vocal learning and sensorimotor control. They share with humans the capacity to adapt vocalizations based on auditory input. Song learning and production are controlled in Songbirds by the song system, which forms a network of interconnected discrete brain nuclei. Here, we use the CUBIC and iDISCO+ protocols for clearing adult Songbird brain tissue. Combined with light sheet imaging, we show the potential of tissue clearing for the investigation of connectivity between song nuclei, as well as for neuroanatomy and brain vasculature studies.
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Data_Sheet_1_Tissue Clearing and Light Sheet Microscopy: Imaging the Unsectioned Adult Zebra Finch Brain at Cellular Resolution.docx
2019Co-Authors: Mariana Diales Rocha, Daniel Normen Düring, Philipp Bethge, Fabian F. Voigt, Staffan Hildebrand, Fritjof Helmchen, Alexander Pfeifer, Richard Hans Robert Hahnloser, Manfred GahrAbstract:The inherent complexity of brain tissue, with brain cells intertwining locally and projecting to distant regions, has made three-dimensional visualization of intact brains a highly desirable but challenging task in neuroscience. The natural opaqueness of tissue has traditionally limited researchers to techniques short of single cell resolution such as computer tomography or magnetic resonance imaging. By contrast, techniques with single-cell resolution required mechanical slicing into thin sections, which entails tissue distortions that severely hinder accurate reconstruction of large volumes. Recent developments in tissue clearing and light sheet microscopy have made it possible to investigate large volumes at micrometer resolution. The value of tissue clearing has been shown in a variety of tissue types and animal models. However, its potential for examining the Songbird brain remains unexplored. Songbirds are an established model system for the study of vocal learning and sensorimotor control. They share with humans the capacity to adapt vocalizations based on auditory input. Song learning and production are controlled in Songbirds by the song system, which forms a network of interconnected discrete brain nuclei. Here, we use the CUBIC and iDISCO+ protocols for clearing adult Songbird brain tissue. Combined with light sheet imaging, we show the potential of tissue clearing for the investigation of connectivity between song nuclei, as well as for neuroanatomy and brain vasculature studies.
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Distribution of aromatase, estrogen receptor, and androgen receptor mRNA in the forebrain of Songbirds and nonSongbirds.
The Journal of comparative neurology, 1999Co-Authors: Reinhold Metzdorf, Manfred Gahr, Leonida FusaniAbstract:Androgens and estrogens are crucial for the differentiation and function of the vocal control system of Songbirds. A major source of estrogens in Songbirds is the cerebral aromatization of circulating testosterone by aromatase (ARO). In the vocal control system, Songbirds have a unique estrogen receptor (ER)-containing area, the nucleus hyperstriatalis ventrale pars caudale (HVC) of the caudal neostriatum. Work in the zebra finch has demonstrated ARO expression adjacent to but not in the HVC. Compared with other Songbirds, such as the canary, the HVC of adult zebra finches contains only few ERs. To determine whether the disjunctive distribution of ERs and ARO in the forebrain is a Songbird-specific feature, the authors investigated ARO and ER mRNA expression in Songbirds (canary, house sparrow, and zebra finch) and in nonSongbirds (budgerigar, ring dove, swift, grey partridge, and barn owl) of five avian orders. In addition, the coexpression of androgen receptor (AR) and ARO mRNAs was studied. Preoptic hypothalamic areas showed similar expression of ARO in all species. In the caudal neostriatum, ARO, AR, and ER transcripts were found only in Songbirds. ARO and ER mRNA expression in the caudal forebrain was spatially separated, i.e., the HVC contained ER mRNA but very little or no ARO mRNA, and the caudomedial neostriatum contained high levels of ARO mRNA but few if any ERs. ARO and AR mRNAs, however, were coexpressed in the caudomedial neostriatum. The coexpression of ARO mRNA with AR mRNA but not with ER mRNA was found in further brain areas, such as the nucleus posterior lateralis hypothalami. The area-specific coexpression of AR, ER, and ARO suggests various possibilities for the steroid-dependent regulation of ARO and for the role of ARO in controlling AR- and ER-dependent mechanisms.
Christopher K. Thompson - One of the best experts on this subject based on the ideXlab platform.
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Cell death and the song control system: A model for how sex steroid hormones regulate naturally‐occurring neurodegeneration
Development growth & differentiation, 2011Co-Authors: Christopher K. ThompsonAbstract:The production, learning, and perception of song in Songbirds are regulated by a series of discrete brain nuclei known as the song control system. In most Songbird species, the song control system is sexually dimorphic, and these dimorphisms become more robust after birds have hatched. In seasonally breeding Songbirds, the song control system grows and regresses depending upon breeding context. The development and seasonal plasticity of the song control system are dependent upon neurodegenerative processes, which can be ameliorated, at least in part, by circulating sex steroid hormones. I will describe two areas of song control system research that have provided important information about how hormonal control of cell death contributes to the shaping of behaviorally-relevant brain circuits. First, sexual dimorphism in the zebra finch song control system is robust and emerges partially due to substantial regression of female song control system nuclei during development. Second, in seasonally-breeding Songbirds, the song control system regresses as birds transition from breeding to non-breeding conditions. In a controlled laboratory setting where hormones can be acutely withdrawn, these brain areas regress in only a matter of hours to days. Taken together, these results demonstrate that the study of cell death in the song control system provides an excellent opportunity for understanding how changes in circulating levels of sex steroids affect the degeneration of hormone-sensitive brain circuits.
