Roles of photoperiod and testosterone in seasonal plasticity of the avian song control system

The song control nuclei of songbirds undergo pronounced seasonal changes in size and neuronal attributes. The mechanisms by which seasonal changes in environmental variables such as photoperiod mediate seasonal changes in these brain regions are not known. Manipulations of photoperiod and/or testosterone in captive songbirds induce seasonal changes in the size of song nuclei comparable to those observed in wild songbirds. It is unclear, however, whether the effects of photoperiod on the song nuclei are mediated by testosterone or by steroid-independent mechanisms. We independently manipulated photoperiod and testosterone in castrated male Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) to determine the contributions of steroid-dependent and -independent actions of photoperiod to seasonal changes in the size and neuronal attributes of song nuclei. Testosterone implants increased the size of several song nuclei, regardless of photoperiod. Photoperiod exerted small but significant steroid-independent effects on the volume of the higher vocal center and the size of neurons in the robust nucleus of the archistriatum. Photoperiod also modulated the effect of testosterone on the size of area X; testosterone treatment had a more pronounced effect on the size of area X on short days than on long days. These results suggest that although testosterone is the primary factor mediating seasonal changes in neural attributes of the song nuclei, photoperiod may act via mechanisms that are independent of steroid levels to supplement or modulate the actions of testosterone. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 426–442, 1997.     

Early life conditions that impact song learning in male zebra finches also impact neural and behavioral responses to song in females

Early life stressors can impair song in songbirds by negatively impacting brain development and subsequent learning. Even in species in which only males sing, early life stressors might also impact female behavior and its underlying neural mechanisms, but fewer studies have examined this possibility. We manipulated brood size in zebra finches to simultaneously examine the effects of developmental stress on male song learning and female behavioral and neural response to song. Although adult male HVC volume was unaffected, we found that males from larger broods imitated tutor song less accurately. In females, early condition did not affect the direction of song preference: all females preferred tutor song over unfamiliar song in an operant test. However, treatment did affect the magnitude of behavioral response to song: females from larger broods responded less during song preference trials. This difference in activity level did not reflect boldness per se, as a separate measure of this trait did not differ with brood size. Additionally, in females we found a treatment effect on expression of the immediate early gene ZENK in response to tutor song in brain regions involved in song perception (dNCM) and social motivation (LSc.vl, BSTm, TnA), but not in a region implicated in song memory (CMM). These results are consistent with the hypothesis that developmental stressors that impair song learning in male zebra finches also influence perceptual and/or motivational processes in females. However, our results suggest that the learning of tutor song by females is robust to disturbance by developmental stress. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018     

鸣禽前端脑通路与鸣唱可塑性

前端脑通路即鸣禽的基底神经节——前脑通路,为鸣唱学习和可塑性所必需。本文综述了前端脑通路的起源、发育、作用及其鸣唱可塑性方面的最新进展。     

Age- and behavior-related variation in volumes of song control nuclei in male European starlings

There is considerable interindividual variation in the volumes of song control nuclei. Sex and physiological condition appear to contribute to these differences; however, these factors alone do not account for all of the variation. Studies have attempted to relate differences in song behavior (i.e., song repertoire size) to variation in song nucleus volume, but have met with mixed success. In this article, two studies are presented that used male European starlings (Sturnus vulgaris) to explore the relationship between song nuclei volumes and age-related differences in song behavior and interindividual variation in song behavior in adults. The results of the first study showed that song repertoire size and song bout length were significantly greater in older adult than in yearling males. In addition, the volumes of the high vocal center (HVC) and nucleus robustus archistriatalis (RA) were significantly larger in older adults than yearlings. Area X of the parolfactory lobe did not differ significantly in volume between the two age classes. In the second study, both HVC and RA volume correlated positively with song bout length but not repertoire size among adult birds. Based on these results a new hypothesis is presented that states that variation in song nuclei volumes in starlings relates more to the amount of song produced than to the number of song types stored in memory. © 1996 John Wiley & Sons, Inc.     

鸣禽发声控制核团内的神经递质及其在发声学习中的作用

神经递质在鸣禽脑中不仅是神经元间信号传递中介物质,还有资料表明它们通过在习鸣敏感期影响发声控制团间的突触联系的形成和突触可塑性,从而对鸣转类型的确定和巩固起重要作用,本文着重介绍了鸣禽发声控制核团内神经递质的分布及变化情况,并就神经递质在发声学习中的作用进行了探讨。     

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? © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 549–571, 1997     

鸣禽发声学习行为的神经生物学机制

鸣禽发声学习的控制系统主要由一条直接神经通路和一条辅助神经通路组成,由前脑控制发声学习的最高中枢ＨＶＣ、旁嗅叶的Ｘ区和巨细胞核外侧部（ｌＭＡＮ）组成的辅助通路,对鸟类发声学习行为的发育和调制具有重要作用。发声控制系统中神经元类型、数量及再生与更替、神经组构及其重组、神经介质和受体的分布等差异,决定了鸣禽在发声学习行为表现的差异以及性双态性。本文对近年鸟类控制发声学习行煌神经生物学机制的进展作了较为     

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. 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

A field study of seasonal neuronal incorporation into the song control system of a songbird that lacks adult song learning

Adult songbirds can incorporate new neurons into HVc, a telencephalic song control nucleus. Neuronal incorporation into HVc is greater in the fall than in the spring in adult canaries (open‐ended song learners) and is temporally related to seasonal song modification. We used the western song sparrow, a species that does not modify its adult song, to test the hypothesis that neuronal incorporation into adult HVc is not seasonally variable in age‐limited song learners. Wild song sparrows were captured during the fall and the spring, implanted with osmotic pumps containing [³H]thymidine, released onto their territories, and recaptured after 30 days. The density, proportion, and number of new HVc neurons were all significantly greater in the fall than in the spring. There was also a seasonal change in the incorporation of new neurons into the adjacent neostriatum that was less pronounced than the change in HVc. This is the first study of neuronal recruitment into the song control system of freely ranging wild songbirds. These results indicate that seasonal changes in HVc neuronal incorporation are not restricted to open‐ended song learners. The functional significance of neuronal recruitment into HVc therefore remains elusive. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 316–326, 1999     

Dynamic gene expression in the song system of zebra finches during the song learning period

The brain circuitry that controls song learning and production undergoes marked changes in morphology and connectivity during the song learning period in juvenile zebra finches, in parallel to the acquisition, practice and refinement of song. Yet, the genetic programs and timing of regulatory change that establish the neuronal connectivity and plasticity during this critical learning period remain largely undetermined. To address this question, we used in situ hybridization to compare the expression patterns of a set of 30 known robust molecular markers of HVC and/or area X, major telencephalic song nuclei, between adult and juvenile male zebra finches at different ages during development (20, 35, 50 days post‐hatch, dph). We found that several of the genes examined undergo substantial changes in expression within HVC or its surrounds, and/or in other song nuclei. They fit into broad patterns of regulation, including those whose expression within HVC during this period increases (COL12A1, COL 21A1, MPZL1, PVALB, and CXCR7) or decreases (e.g., KCNT2, SAP30L), as well as some that show decreased expression in the surrounding tissue with little change within song nuclei (e.g. SV2B, TAC1). These results reveal a broad range of molecular changes that occur in the song system in concert with the song learning period. Some of the genes and pathways identified are potential modulators of the developmental changes associated with the emergence of the adult properties of the song control system, and/or the acquisition of learned vocalizations in songbirds. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1315–1338, 2015     

Developmental shifts in gene expression in the auditory forebrain during the sensitive period for song learning

A male zebra finch begins to learn to sing by memorizing a tutor's song during a sensitive period in juvenile development. Tutor song memorization requires molecular signaling within the auditory forebrain. Using microarray and in situ hybridizations, we tested whether the auditory forebrain at an age just before tutoring expresses a different set of genes compared with later life after song learning has ceased. Microarray analysis revealed differences in expression of thousands of genes in the male auditory forebrain at posthatch day 20 (P20) compared with adulthood. Furthermore, song playbacks had essentially no impact on gene expression in P20 auditory forebrain, but altered expression of hundreds of genes in adults. Most genes that were song‐responsive in adults were expressed at constitutively high levels at P20. Using in situ hybridization with a representative sample of 44 probes, we confirmed these effects and found that birds at P20 and P45 were similar in their gene expression patterns. Additionally, eight of the probes showed male–female differences in expression. We conclude that the developing auditory forebrain is in a very different molecular state from the adult, despite its relatively mature gross morphology and electrophysiological responsiveness to song stimuli. Developmental gene expression changes may contribute to fine‐tuning of cellular and molecular properties necessary for song learning. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009     

Steroid accumulation in song nuclei of a sexually dimorphic duetting bird,the rufous and white wren

This study tested the hypothesis that the relative proportion of neurons that are hormone sensitive in avian song control nuclei is related to the basic motor ability to sing, whereas the absolute number of such neurons is related to the complexity of song behavior. Either [³H]testosterone (T) or estradiol (E₂) was injected into male and female rufous and white wrens (Thryothorus rufalbus), a tropical species in which females sing duets with males but have smaller song repertoires than males. Autoradiographic analysis indicated that there were no sex differences in the proportions of T or E₂ target cells in two song nuclei: the high vocal center (HVC) and the lateral portion of the magnocellular nucleus of the anterior neostriatum (IMAN). The density of labeled cells per unit volume of tissue did not differ between the sexes in either song nucleus. Males have larger song nuclei, however, which is consistent with their more complex song behavior, and therefore have a greater total number of hormone-sensitive neurons in these regions than do females. Comparison of these results with measures of hormone accumulation in zebra finches, canaries, and bay wrens supports the hypothesis presented. © 1996 John Wiley & Sons, Inc.     

Lateralization and motor stereotype of song production in the brown-headed cowbird

Song production in adult brown-headed cowbirds(Molothrus ater ater) is lateralized, with a slight right syringeal dominance. The left size of the syrinx produces low-frequency (200–2000 Hz) notes within the introductory note clusters, while the right side produces the higher-frequency (1500–6000 Hz) introductory notes, the interphrase unit (10–12 kHz), and the final high-frequency whistle (5–13 kHz). Cross-correlation analyses reveal that individual cowbirds produce each of their four to seven song types with a distinct stereotyped motor pattern–as judged by the patterns of syringeal airflow and subsyringeal pressure. The acoustic differences across song types are reflected in the differences in the bronchial airflow and air sac pressure patterns associated with song production. These motor differences are particularly striking within the second and third introductory note clusters where there is a rapid switching back and forth between the two sides of the syrinx in the production of notes. These motor skills may be especially important in producing behaviorally effective song. 1994 John Wiley & Sons, Inc.     

HVC lesions modify immediate early gene expression in auditory forebrain regions of femalesongbirds

It is well established that auditory forebrain regions of oscine birds are essential for the encoding of species‐typical songs and are, therefore, vital for recognition of song during sociosexual interactions. Regions such as the caudal medial nidopallium (NCM) and the caudal medial mesopallium (CMM) are involved in perceptual processing of song and the formation of auditory memories. There is an additional telencephalic nucleus, however, that has also been implicated in species recognition. This nucleus is HVC, a prominent nucleus that sits at the apex of the song system, and is well known for its critical role in song learning and song production in male songbirds. Here, we explore the functional relationship between auditory forebrain regions (i.e., NCM and CMM) and HVC in female canaries (Serinus canaria). We lesion HVC and examine immediate early gene responses to conspecific song presentation within CMM and NCM to explore whether HVC can modulate auditory responses within these forebrain regions. Our results reveal robust deficits in ZENK‐ir in CMM and NCM of HVC‐lesioned females when compared with control‐ and sham‐lesioned females, indicating that functional connections exists between HVC and NCM/CMM. Although these connected regions have been implicated in song learning and production in males, they likely serve distinct functions in female songbirds that face the task of song recognition rather than song production. Identifying functional connections between HVC and auditory regions involved in song perception is an essential step toward developing a comprehensive understanding of the neural basis of song recognition. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013     

Annual cycle of the black‐capped chickadee: Seasonality of singing rates and vocal‐control brain regions

Black‐capped chickadees have a rich vocal repertoire including learned calls and the learned fee‐bee song. However, the neural regions underlying these vocalizations, such as HVC, area X, and RA (robust nucleus of arcopallium), remain understudied. Here, we document seasonal changes in fee‐bee song production and show a marked peak in singing rate during March through May. Despite this, we found only minimal seasonal plasticity in vocal control regions of the brain in males. There was no significant effect of time of year on the size of HVC, X, or RA in birds collected in January, April, July, and October. We then pooled birds into two groups, those with large testes (breeding condition) and those with small testes (nonbreeding), regardless of time of year. Breeding birds had slightly larger RA, but not HVC or X, than nonbreeding birds. Breeding birds had slightly larger HVC and RA, but not X, as a proportion of telencephalon volume than did nonbreeding birds. Birds collected in July had heavier brains than birds at other times of year, and had the greatest loss in brain mass during cryoprotection. The absence of any overall seasonal change in the vocal‐control regions of chickadees likely results from a combination of individual differences in the timing of breeding phenology and demands on the vocal‐control regions to produce learned calls year‐round. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Functional organization of forebrain pathways for song production and perception

This article reviews the organization of the forebrain nuclei of the avian song system. Particular emphasis is placed on recent physiologic recordings from awake behaving adult birds while they sing, call, and listen to broadcasts of acoustic stimuli. The neurons in the descending motor pathway (HVc and RA) are organized in a hierarchical arrangement of temporal units of song production, with HVc neurons representing syllables and RA neurons representing notes. The nuclei Uva and NIf, which are afferent to HVc, may help organize syllables into larger units of vocalization. HVc and RA are also active during production of all calls. The patterns of activity associated with calls differ between learned calls and those that are innately specified, and give insight into the interactions between the forebrain and midbrain during calling, as well as into the evolutionary origins of the song system. Neurons in Area X, the first part of the anterior forebrain pathway leading from HVc to RA, are also active during singing. Many HVc neurons are also auditory, exhibiting selectivity for learned acoustic parameters of the individual bird's own song (BOS). Similar auditory responses are also observed in RA and Area X in anesthetized birds. In contrast to HVc, however, auditory responses in RA are very weak or absent in awake birds under our experimental paradigm, but are uncovered when birds are anesthetized. Thus, the roles of both pathways beyond HVc in adult birds is under review. In particular, theories hypothesizing a role for the descending motor pathway (RA and below) in adult song perception do not appear to obtain. The data also suggest that the anterior forebrain pathway has a greater motor role than previously considered. We suggest that a major role of the anterior forebrain pathway is to resolve the timing mismatch between motor program readout and sensory feedback, thereby facilitating motor programming during birdsong learning. Pathways afferent to HVc may participate more in sensory acquisition and sensorimotor learning during song development than is commonly assumed. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 671–693, 1997     

The integration of song environment by catecholaminergic systems innervating the auditory telencephalon of adult female European starlings

Mate choice is among the most consequential decisions a sexually reproducing organism can make. In many songbird species, females make mate-choice decisions based, in part, on variation between males in songs that reflect their quality. Importantly, females may adjust their choice relative to the prevalence of high quality songs. In European starlings (Sturnus vulgaris), females prefer males that primarily sing long songs over those that primarily sing short songs, and sensitivity of the auditory telencephalon to song length depends on the prevalence of long songs in the environment. Several lines of evidence suggest a role for noradrenergic innervation of the auditory telencephalon in mediating this neuro- and behavioral plasticity. To simulate variation in quality of the song environment, we exposed adult female starlings to 1 week of either long or short songs and then quantified several monoamines and their metabolites in the caudomedial mesopallium and caudomedial nidopallium (NCM) using high performance liquid chromatography. We also used immunocytochemistry to assess these areas for immunoreactive dopamine-beta-hydroxylase (DBH-ir), the enzyme that synthesizes norepinephrine. We found that long songs elevated levels of the principal norepinephrine metabolite, the principal dopamine metabolite, and the probability of DBH-ir in the NCM compared to short songs. Song environment did not appear to influence norepinephrine or dopamine levels. Thus, the quality of the song environment regulates the local secretion of catecholamines, particularly norepinephrine, in the female auditory telencephalon. This may form a basis for plasticity in forebrain sensitivity and mate-choice behavior based on the prevalence of high-quality males.     

Temporal gene expression profile after acute electroconvulsive stimulation in the rat

Electroconvulsive therapy (ECT) remains one of the most effective treatments of major depression. It has been suggested that the mechanisms of action involve gene expression. In recent decades there have been several investigations of gene expression following both acute and chronic electroconvulsive stimulation (ECS). These studies have focused on several distinct gene targets but have generally included only few time points after ECS for measuring gene expression. Here we measured gene expression of three types of genes: Immediate early genes, synaptic proteins, and neuropeptides at six time points following an acute ECS. We find significant increases for c-Fos, Egr1, Neuritin 1 (Nrn 1), Bdnf, Snap29, Synaptotagmin III (Syt 3), Synapsin I (Syn 1), and Psd95 at differing time points after ECS. For some genes these changes are prolonged whereas for others they are transient. Npy expression significantly increases whereas the gene expression of its receptors Npy1r, Npy2r, and Npy5r initially decreases. These decreases are followed by a significant increase for Npy2r, suggesting anticonvulsive adaptations following seizures. In summary, we find distinct changes in mRNA quantities that are characteristic for each gene. Considering the observed transitory and inverse changes in expression patterns, these data underline the importance of conducting measurements at several time points post-ECS.     

c-fos Expression in Gracilothalamic Tract Neurons after Electrical Stimulation of the Injured Sciatic Nerve in the Adult Rat

The number of c-fos protein-like immunoreactive (Fos-LI) cells in the gracile nucleus was determined after electrical stimulation at Aα/Aβ-fiber strength of the normal and of the previously injured sciatic nerve in adult rats. No Fos-LI cells were seen after electrical stimulation of the noninjured sciatic nerve, or after sciatic nerve injury without electrical stimulation. However, stimulation 21 days after sciatic nerve transection resulted in numerous Fos-LI cells in the ipsilateral gracile nucleus. Combined Fos immunocytochemistry and retrograde labeling from the thalamus showed that the majority (76%; range = 70–80%) of the cells in the gracile nucleus that expressed Fos-LI after nerve injury projected to the thalamus. The results indicate that morphological, biochemical, and physiological alterations in primary sensory central endings and second-order neurons, which have earlier been demonstrated in the dorsal column nuclei after peripheral nerve injury, are accompanied by changes in the c-fos gene activation pattern after stimulation of the injured sciatic nerve. A substantial number of the c-fos-expressing neurons project to the thalamus.