Central DSP-4 treatment decreases norepinephrine levels and courtship behavior in male zebra finches

In zebra finches, gonadal steroids activate male courtship, including singing, and also strongly modulate norepinephrine (NE) levels and turnover in brain areas regulating courtship behavior. In a previous study, systemic administration of DSP-4 caused significant decreases in courtship singing. These behavioral decrements were correlated with the degree of NE depletion in several vocal control nuclei. In the present study, we attempted to further decrease brain NE levels while minimizing systemic effects by infusing DSP-4 directly into the third ventricle. DSP-4 treatment significantly reduced NE levels in three of six vocal control nuclei and both hypothalamic nuclei sampled without significantly altering dopamine or serotonin levels in any areas. DSP-4-treated males took longer to begin singing and performed fewer song bouts and courtship displays. Interestingly, behavioral deficits were limited to courtship song displays, other behavior patterns, including female-directed behaviors like approach and follow, were unaffected by DSP-4 treatment. DSP-4 treatment appeared to affect singing behavior by causing deficits in initial attentiveness to females and initiation of singing rather than by affecting song structure.     

Transient expression and transport of brain-derived neurotrophic factor in the male zebra finch's song system during vocal development

The distribution of brain-derived neurotrophic factor (BDNF) in the song system of male zebra finches changes with posthatching age. At day 20, the hyperstriatum ventrale, pars caudale is the only song nucleus in which neurons showed BDNF immunoreactivity. At day 45, the staining in hyperstriatum ventrale, pars caudale was denser than at day 20 and the robust nucleus of the archistriatum, another song nucleus, showed BDNF labeling. By day 65, two additional song nuclei, area X and the lateral magnocellular nucleus of the anterior neostriatum, have become immunoreactive. In the adult, however, the amount of BDNF labeling in all of these brain nuclei is sharply reduced. These sequential events, the anatomical connections between these song nuclei, and the labeling of relevant axons and terminals suggest anterograde transport of BDNF. Furthermore, the timing of BDNF expression coincident with the development of singing behavior suggests that this neurotrophin may be directly involved with the differentiation of the song system.     

Sex difference in the size of the neural song control regions in a dueting songbird with similar song repertoire size of males and females

Previous studies have suggested a causal relation between sex differences in behavior such as singing and sex differences in the size of brain areas such as the forebrain song control areas of songbirds. In the present study we show that the size of the forebrain vocal control areas nucleus hyperstriatalis ventrale pars caudale (HVC) and nucleus robustus archistriatalis (RA) and its neuron numbers are about twice as large in males as in females of the African dueting bush shrike Laniarius funebris. However, song types are of similar complexity (number of elements per song type, physical properties of elements) in both sexes, and repertoire size does not differ between males and females. Furthermore, in captivity male and female shrikes are able to learn the same song types. This demonstrates for the shrike that sex differences in the size of vocal control areas and in its neuron numbers do not predict the type of sex-typical vocal behavior. This result is supported by a statistical comparison of the sex differences in HVC size, RA size, and song repertoire size of all songbird species studied to date. Sex differences in species in which only the males sing are indeed larger than in species in which the females also sing; in songbird species with singing females, however, the sex differences in HVC and RA volume appear to be independent of the vocal repertoire size of females. The songbird model therefore does not support the notion that sex differences in area size and neuron number explain sex differences in a behavior that occurs in both sexes. Furthermore, in the shrike, neuron soma size is similar in males and females in the song motonucleus hypoglossus pars tracheosyringealis (nXIIts) and in the premotor nucleus RA, but is sexually dimorphic in the higher vocal center HVC. Thus, male and female shrikes produce songs of similar complexity with different neuron phenotypes.     

Social Suppression of Song Is Associated With a Reduction in Volume of a Song-Control Nucleus in European Starlings (Sturnus vulgaris).

In seasonally breeding songbirds, variations in testosterone and song correlate with volume changes in brain nuclei associated with song, including the HVC. The authors tested whether singing can lead to activity-dependent increases in HVC volume by examining song output in starlings (Sturnus vulgaris). The authors manipulated males' environments so that only some were dominant with nestboxes, whereas others were not. Some of these males thus sang at higher rates and had larger HVC volume than others. The study was conducted over 2 years. In 1 year, males selectively occupied nestboxes but did not sing. HVC volume did not differ in these starlings, indicating that nestbox possession alone cannot increase HVC. The findings suggest that changes in song nuclei volume can be driven by changes in singing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions to the medial preoptic nucleus differentially affect singing and nest box-directed behaviors within and outside of the breeding season in European starlings (Sturnus vulgaris).

Little is known about how the brain regulates context-appropriate communication. European starlings produce song in various social contexts. During the breeding season, males with nest sites sing high levels of sexually motivated song in response to a female. Outside of this context, song rates are not affected by female presence. The medial preoptic nucleus (POM) regulates male sexual behavior, and studies in songbirds implicate the POM in sexually motivated song. Recent data suggest that the role of the POM might extend to song produced in other contexts as well. To examine this possibility, effects of bilateral electrolytic lesions of the POM on singing and other behaviors in adult male starlings within sexually relevant and nonsexual contexts were studied. Lesions to the POM exclusively reduced song and nest box-directed behaviors within highly sexually relevant contexts. Unexpectedly, POM lesions increased song in a nonsexual context, suggesting an inhibitory role for the POM in this context. These data suggest that the POM interacts with the song control system so that song occurs in an appropriate social context in response to appropriate stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of gene regulation in song circuit development and song learning

The songbird has emerged as an important model for study of brain-behavior relationships by virtue of its rich natural advantages and from the pioneering efforts of explorers using anatomical and behavioral approaches. Now, molecular biology is providing a new and complementary paradigm for discerning songbird brain organization and function. Here, I review the work over the last 10 years that has laid the foundation for approaching songbird biology from the molecular perspective. As a result of this work, specific hypotheses can now be framed and tested regarding the mechanisms behind song circuit formation, behavioral plasticity, and the boundaries of adaptability. Age-related changes in more than 15 molecules have been observed in the song system of juvenile zebra finches, and these changes seem to define specific phases in circuit development. In adult songbirds, ordinary song-related activities such as singing and listening cause dramatic increases in gene expression in brain areas specific to each activity. The sensitivity of gene activation is modulated as a result of experience in adulthood and also changes during juvenile song learning. These studies have provided unexpected insights into the functional organization of the song circuit and the potential role of extrinsic modulatory systems in directing and limiting plastic change in the brain. With this rich base of knowledge, and techniques of gene manipulation on the horizon, answers to old questions seem within our reach: What sets the boundaries of neural plasticity? What limits learning?     

Photodynamic therapy for rheumatoid arthritis?

Songbirds have emerged as extremely important animals for investigating sex steroid hormone effects on the central nervous system. The masculinizing effects of exogenous estrogen on the neural circuits controlling song in female zebra finches are well documented. There is evidence that estrogens are necessary for the full activation of singing behavior in several species. These kinds of studies have led us and others to investigate the mechanisms whereby estrogens are made available to the brains of songbirds during development and adulthood. In this article, I review results of some of these studies examining the estrogen synthetic enzyme aromatase and its expression and activity in brain and in other tissues of songbirds. I will discuss some results and thoughts we have about the interactions of aromatase with the two remaining androgen-metabolizing enzymes in the avian brain, 5alpha-reductase, the enzyme that converts T into the active androgen 5alpha-dihydrotestosterone (DHT); and 5beta-reductase, the enzyme that converts T into the inactive 5beta-DHT. Finally, I will consider some ideas raised by these studies concerning potential sources of the androgen substrate for brain aromatization as well as some possible new functions that aromatase might be playing in the songbird telencephalon.     

Role of auditory feedback in canary song development.

Describes studies conducted with an inbred strain of Belgian "Wasserschlager" canaries bred selectively by aviculturalists in Europe for particular patterns of singing behavior. As in other songbirds, early deafening had drastic effects on the song of the roller canary, a caudueline finch, resulting in a song that was much simpler and more variable than the normal. The repertoire of syllable types was reduced from 30 to a mean of 5.0. Loud white noise was successfully used as a reversible method of cutting off auditory feedback from vocal behavior. Although suffering permanent elevation of hearing thresholds, Ss reared in noise to 200 days, singing at first like deaf Ss, subsequently increased their syllable repertoires significantly. Ss reared in noise to weaning at 40 days, again partly deaf, achieved a normal repertoire size when stimulated with a singing adult. Without such stimulation the repertoire was significantly reduced, showing that canary song is not fully innate. Although abnormal, the song of deaf canaries retained more species-specific features than did the song of emberizine sparrows when the songs developed without auditory feedback. Results are interpreted in terms of a sensory template theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factors contributing to the reduction of stuttering during singing

This study was conducted to determine if the reduction of stuttering typically observed during singing is associated with altered vocalization or the familiarity of the melody and lyrics of the song sung by the stutterer, or both. Subjects were eight adult male stutterers. Prior to testing, each of these individuals demonstrated that he knew the melody and lyrics of a well-known song from memory. Subsequently, subjects were asked to read these lyrics aloud and then sing them. Next, subjects had to read aloud and then sing a set of unfamiliar lyrics to the conventional melody of the same song. The stutterers' reading and singing performances were audiotaped. The dependent measures of utterance duration and stuttering frequency were extracted from the tapes. Results showed that subjects' utterance durations were significantly longer during singing than reading. The main effects of singing and familiarity were both associated with significant reductions in stuttering frequency. The greatest decrement in stuttering occurred in the condition where subjects sang the familiar melody and lyrics. These findings were interpreted to mean that changes in vocalization cannot account for all of the decrease in stuttering that occurs during singing. During song, the familiarity of the melody and lyrics being produced may also affect stuttering frequency.     

Brain space for a learned task

Forty-six adult male and female canaries were sacrificed, their brains were weighed and the volume of several brain nuclei reconstructed from the cresyl violet-stained material. Two forebrain vocal control nuclei, hyperstriatum ventrale, pars caudale (HVc) and nucleus robustus archistriatalis (RA), were approximately 4 and 3 times larger, respectively, in males than in females, confirming previous findings. There was no consistent right-left asymmetry in the volume of these nuclei in males and females. Twenty-five male birds in this study had their song repertoire recorded during the peak of the singing season. They were sacrificed 3 to 4 months later. The size of the song repertoire, measured as number of different syllable types, showed a positive and significant correlation with the size of HVc and RA. There was no significant correlation between size of the syllable repertoire and age, brain weight or the volume of two brain nuclei not involved in song control. This is the first time that the amount of brain allotted to a specific learned skill has been shown to correlate positively with the amount of that skill that is learned. Interestingly, too, there was a positive and significant correlation between testis weight at the end of the breeding season and the volume of RA at that time, suggesting a hormone-mediated seasonal modulation of part of the brain space occupied by song control pathways. This material seems well suited for studying the relation between space and learning, and the manner in which this relation is influenced by gonadal hormones.     

Management of the patient with sickle cell disease

A discrete neural circuit mediates the production of learned vocalizations in oscine songbirds. Although this circuit includes some bilateral pathways at midbrain and medullary levels, the forebrain components of the song control network are not directly connected across the midline. There have been no previous reports of bilateral projections from medullary and midbrain vocal control nuclei back to the forebrain song system, but the existence of such bilateral corollary discharge pathways was strongly suggested by the recent observation that unilateral stimulation of a forebrain song nucleus during singing leads to a rapid readjustment of premotor activity in the contralateral forebrain. In the present study, we used neuroanatomical tracers to demonstrate bilateral projections from (a) the rostral ventrolateral medulla (RVL), which may control respiratory aspects of vocalization, to nucleus uvaeformis (Uva), and (b) the dorsomedial intercollicular nucleus (DM), a midbrain vocal control region, to Uva. Both RVL and DM receive descending projections from the forebrain song nucleus robustus archistriatalis, and Uva projects directly to the forebrain song nuclei interfacialis and high vocal center. We suggest that the bilateral feedback projections from DM and RVL to Uva function to coordinate the two hemispheres during singing in adult songbirds and to convey internal feedback of premotor signals to the forebrain in young birds that are learning to sing.     

Evidence for Opioid Involvement in the Regulation of Song Production in Male European Starlings (Sturnus vulgaris).

Many social animals vocalize at high rates, suggesting that vocal communication is highly motivated and rewarding. In songbirds, much is known about the neural control of vocal behavior; however, little is known about neurobiological mechanisms regulating the motivation to communicate. This study examined a possible role for opioid neuropeptides in motivation and reward associated with song production in male European starlings (Sturnus vulgaris). Peripheral opioid blockade facilitated male song production. Furthermore, methionine-enkephalin immunolabeled fiber densities within brain regions in which opioids are known to regulate motivation and reward (i.e., the medial preoptic nucleus and ventral tegmental area) related positively to male song production. These data suggest that song production might be regulated by opioid activity within motivation and reward neural systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Melatonin binding in the house sparrow song control system: sexual dimorphism and the effect of photoperiod

Avian song is a sexually dimorphic behavior which is regulated seasonally. This regulation involves the construction and growth of song control structures: the high vocal center (HVC), nucleus robustus archistrialis (RA), nucleus magnocellularis anterior (MAN), and Area X. Song behavior and its neural correlates are controlled by steroid-dependent and independent processes. The avian circadian system is known to be involved in both daily processes and seasonal reproduction. A major part of this system is the circadian secretion of melatonin by the pineal gland. To determine possible interactions of the circadian and song control systems, the distribution and density of 2-[125I]iodomelatonin (IMEL) binding, an indicator of melatonin sensitivity, were determined in male and female house sparrow brains. Specific binding was found in visual system centers of both genders, but binding in HVC, RA, and Area X was present only in males. Binding in MAN was present in both sexes. Although the effects of short and long photoperiods on male house sparrow IMEL binding in song structures revealed no systematic changes, there were significant differences in binding under different photoperiods in HVC and RA. IMEL binding in the tectofugal nucleus rotundus, however, was consistently highest under short day conditions. IMEL binding in song control nuclei was independent of testicular influence, since castration did not affect it significantly. The data point to a role for the circadian system of house sparrows in song control, but a specific role for melatonin in the daily or seasonal regulation of the song control system in birds, could not be determined.     

Preference for infant-directed singing in 2-day-old hearing infants of deaf parents.

L. J. Trainor (1996) reported preferences for infant-directed versus infant-absent singing in English in 4–7-month-old hearing infants of English-speaking hearing parents. In this experiment, the author tested preferences for infant-directed singing versus adult-directed singing in 15 two-day-old hearing infants of deaf parents for a Japanese and an English play song. Using a modified visual-fixation-based auditory-preference procedure, the author found that infants looked longer at a visual stimulus when looking produced infant-directed singing as opposed to adult-directed singing. These results suggest that infants prefer infant-directed singing over adult-directed singing and that the preference is present from birth and is not dependent on any specific prenatal or postnatal experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interhemispheric coordination of premotor neural activity during singing in adult zebra finches

The song system, a neural network that mediates the learning and production of song by oscine songbirds, is investigated extensively as a model system for understanding the neural basis of complex skill learning. Part of the complexity of birdsong arises from the coordinated recruitment of multiple groups of muscles on both sides of the body. Although the song system is bilaterally organized, little is known about how premotor activities on the two sides are coordinated during singing. We investigated this by unilaterally recording neural activity in the forebrain song nucleus HVc (also known as the high vocal center) during singing and by forcing the premotor activities in the two hemispheres out of synchrony by perturbing neural activity in the contralateral HVc with electrical stimulation. Perturbing the activity in one HVc at any time during a song led to a short-latency readjustment of activity in the contralateral HVc. This readjustment consisted of a true resetting of the temporal pattern of activity in the contralateral HVc rather than merely a transient activity suppression overlaid on an unaltered pattern of premotor activity. These results strongly suggest that the output of song premotor areas in the forebrain is continuously monitored and that an active mechanism exists for resynchronizing the outputs from the two hemispheres whenever their gross temporal patterns differ significantly. The possible anatomical substrates for these coordinating mechanisms and their potential roles in song learning are discussed.     

Regulation of insulin-like growth factor I (IGF-I) gene expression in brain of transgenic mice expressing an IGF-I-luciferase fusion gene

Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5-4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77-388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.     

Axonal connections of the medial magnocellular nucleus of the anterior neostriatum in zebra finches

The medial magnocellular nucleus of the anterior neostriatum (mMAN) is a small cortical nucleus which was previously identified as a component of the neural circuitry controlling vocal behavior in songbirds based on its efferent connection to the High Vocal Center (HVC), a major song control nucleus (Nottebohm et al. [1982] J. Comp. Neurol. 207:344-357; Bottjer et al. [1989] J. Comp. Neurol. 279:312-326). We have conducted tract tracing experiments (using wheat-germ agglutinin-horseradish peroxidase (WGA-HRP), the carbocyanine dye DiI, and biocytin) to determine the complete pattern of afferent and efferent connections of mMAN in adult male zebra finches. We confirmed the existence of an efferent projection from mMAN to HVC and discovered a novel projection to the region medial to caudal HVC called paraHVC (pHVC). Injections of retrograde tracers into mMAN showed that afferent input to mMAN originates from the dorsomedial nucleus of the posterior thalamus (DMP). Injections of DiI into DMP produced anterograde label over mMAN, thus confirming the DMP-to-mMAN projection. Interestingly, this anterograde label extended beyond the region of mMAN defined by HVC-projecting neurons into the immediately surrounding cortex. This extended terminal field of DMP efferents indicates that mMAN encompasses a core population of projection neurons surrounded by a shell of non-HVC-projecting neurons, both of which receive input from the dorsal thalamus. Analysis of retrograde DiI label resulting from DMP injections revealed two major sources of afferent input to DMP originating in regions of the archistriatum and hypothalamus. Inputs to DMP were distributed throughout the dorsal archistriatum and included the area that receives a projection from the parvicellular shell region of the lateral magnocellular nucleus of the anterior neostriatum, a song control nucleus, as well as the dorsal portion of the robust nucleus of the archistriatum, the motor-cortical output of the song control system. The projections from song control regions of the archistriatum to DMP may feed information back into telencephalic song control circuitry via the DMP-->mMAN-->HVC/pHVC pathway. The other source of afferent input to DMP is located in the external cellular stratum of the lateral hypothalamus (SCE). This newly delineated SCE-->DMP-->mMAN-->HVC/pHVC pathway is the first report of a hypothalamic brain region neuroanatomically integrated with song control circuitry. Because hypothalamic brain regions are important for homeostasis and regulating behavior, the trans-synaptic circuitry of mMAN may help to integrate information about the bird's internal state, such as sexual maturation, with song learning and production.     

Differential responding to spring and fall song in mockingbirds (Mimus polyglottos).

Field experiments examined whether mockingbirds respond differently to the distinct acoustical features of spring and fall song. Playback of both spring and fall song produced agonistic responses among 35 Ss during both the spring and the fall. However, significantly more response occurred during playback of spring song, even when spring song was played in the fall. This consistent cross-season difference in responding suggests that the distinctive features of the conspecific songs, not the physiological state of the Ss, were responsible for the response differences. The greater effectiveness of spring song in both the spring and the fall indicates that species-typical features evoking aggression are less pronounced or are reduced in fall song. Data provide indirect evidence that spring song may be the more effective territorial signal. Following playback of spring song in the spring only, the frequency of singing increased substantially. This result suggests that the elaborate song normally produced during the spring may function in territorial pronouncement. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)