鸣禽前脑X区结构功能的研究进展

鸣禽鸣唱与人类说话一样,都是在教习和听觉反馈下形成的感知运动学习过程。鸣禽鸣唱的发育和成熟巩固依赖于发声通路和前端脑通路组成的鸣唱系统的完整。前端脑通路中的X区在鸣唱学习记忆中扮演着重要角色。本文就X区的形态组织结构、在鸣唱发育与成熟巩固中的作用、突触可塑性的研究进展进行了综述,并且将X区与哺乳动物基底神经节的学习记忆功能做了比较。     

新纹状体巨细胞核外侧部（LMAN）与鸣禽鸣唱学习可塑性

鸣禽鸣唱控制系统的前端脑通路（anterior forebrain pathway, AFP）在鸣唱学习中发挥着重要作用。新纹状体巨细胞核外侧部（lateral magnocellular nucleus of the anterior neostriatum, LMAN）是AFP的最后一级输出核团,AFP中的信号通过LMAN传导到弓状皮质栎核（robust nucleus of the arcopallium, RA）,与高级发声中枢（high vocal centre,HVC）共同调节RA的活动,从而影响鸣禽的发声行为。LMAN可能通过其与RA的单突触连接来影响鸣唱可塑性。文章对近年来LMAN在鸣唱学习可塑性方面的研究进行综述。     

新纹状体巨细胞核外侧部与鸣禽鸣唱学习可塑性

鸣禽鸣唱控制系统的前端脑通路(anterior forebrain pathway,AFP)在呜唱学习中发挥着重要作用.新纹状体巨细胞核外侧部(lateral magnocellular nucleus of the anterior neostriatum,LMAN)是AFP的最后一级输出核团,AFP中的信号通过LMAN传导到弓状皮质栎核(robust nucleus of the arcopallium,RA),与高级发声中枢(high vocal centre,HVC)共同调节RA的活动,从而影响鸣禽的发声行为.LMAN可能通过其与RA的单突触连接来影响鸣唱可塑性.文章对近年来LMAN在呜唱学习可塑性方面的研究进行综述.     

中脑多巴胺能神经元与鸣禽鸣唱行为

多巴胺(DA)与鸣禽的鸣唱行为密切相关.多巴胺能神经元主要分布于中脑VTA和SNc以及PAG,它们投射到前端脑鸣唱控制核团,调节鸣唱的学习和产生.研究表明,环境的改变会影响成鸟的鸣唱产生和幼鸟的鸣唱学习,而这种环境依赖性的鸣唱行为变化是由中脑内多巴胺能神经元的活动来介导的.本文重点介绍了近年来有关中脑多巴胺能神经元活动与鸣唱行为关系的研究进展.     

脑源性神经营养因子对鸟类鸣唱行为的调控作用

鸟类鸣唱是一种复杂的发声行为,需要感知和运动技能学习等神经过程的参与。与人类语言学习的过程相似,鸟类鸣唱学习过程由脑中的一整套神经结构所控制,我们称之为鸣唱控制系统。研究表明,脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)在鸣唱控制系统对鸣唱行为的调控中起着关键作用。目前已在BDNF对鸟类鸣唱调控作用的研究方面取得了一批重要的理论成果,主要集中在BDNF影响新生神经元募集及存活、性激素及性别二态性、鸣唱控制系统季节可塑性和鸣曲形成等科学问题。文章对BDNF与鸣唱行为调控关系研究中所取得的进展做了详细论述。     

性激素对成年鸣禽鸣唱可塑性的影响

鸣禽在成年之后表现出广泛的鸣唱行为可塑性变化,其中与季节相关的可塑性变化最为突出.季节可塑性变化与呜禽体内的睾酮水平相关,并伴随鸣唱控制核团的生长或萎缩.研究显示,睾酮的代谢产物与其靶受体结合后,能诱导激素敏感基因表达,其表达产物能促进新生神经元的存活和突触形成,改变鸣唱控制核团的细胞兴奋性和突触传递,从而引起鸣唱行为变化.主要综述性激素对成年鸣禽鸣唱行为以及鸣唱系统可塑性变化的影响以及有关分子细胞机制的研究进展.     

雄激素对成年雄性斑胸草雀前脑高级发声中枢-弓状皮质栎核通路长时程压抑的影响

雄激素可通过调控鸣唱控制系统改变鸣禽的鸣唱行为。本研究以成年雄性斑胸草雀为实验动物,采用在体电生理实验方法,观察雄激素对高级发声中枢(high vocal center,HVC)-弓状皮质栎核(robust nucleus of the arcopallium,RA)通路突触可塑性的影响,以期阐明雄激素对成年鸣禽鸣唱稳定性维持的神经生理机制。将实验动物分为对照组、去势组与去势+埋植睾酮组,分别记录高频刺激(400 Hz,2 s)HVC后,HVC-RA通路长时程压抑(long-term depression,LTD)的变化以及双脉冲易化效应。结果显示,高频刺激HVC,在对照组可以记录到LTD现象;去势组中仅有短时程压抑(short-term depression,STD)现象;去势+埋植睾酮组中LTD现象则恢复。双脉冲易化现象在去势组不明显,而对照组和去势+埋植睾酮组易化率明显高于去势组。以上结果提示,雄激素可能通过影响成年雄性斑胸草雀HVC-RA通路的LTD水平来维持鸣曲稳定性,并对该通路的短时程突触可塑性有一定的调节作用。     

鸟鸣及其鸣唱控制系统发育可塑性研究进展

鸟类的鸣唱控制系统已成为研究神经系统与学习、行为和发育相关的一个重要模型。鸣禽鸣唱学习行为的神经基础为脊椎动物复杂习得行为的解剖学功能定位提供了一个范例。它也可为我们研究人类语言学习记忆提供借鉴,对近年来在鸟类鸣唱及其呜唱控制系统发育可塑性方面的研究进展进行了综述。     

鸣禽端脑发声运动通路的电生理学特性

鸣禽是除了人类以外极少数具有发声信号学习能力的动物,其已成为研究运动序列控制和学习记忆神经过程的理想模型。鸣禽端脑中的高级发声中枢(high vocal center)、弓状皮质栎核(robust nucleus of the arcopallium)和脑干中的运动核团构成了控制发声的运动通路。该文对鸣禽端脑发声运动通路的电生理学特性及其在发声控制和鸣唱学习中的作用进行了全面的分析综述。     

成年鸟脑神经更替研究进展

成年脊椎动物脑中仍有自发神经更替现象的存在.新生神经元的类型,神经更替的过程及其影响因素,都与中枢神经系统的可塑性有密切的关系.成体神经发生、神经更替和脑的干细胞生物学将使分子生物学和临床医学得到长足的发展.不用通过外源细胞的移植,就能达到良好的治疗效果,尤其是某些神经退化病和中枢神经系统损伤.主要对以鸣禽鸣唱系统为模型的成年鸟脑神经发生及神经更替进行了综述.     

Song tutoring triggers CaMKII phosphorylation within a specialized portion of the avian basal ganglia

In several songbird species, a specialized anterior forebrain pathway (AFP) that includes part of the avian basal ganglia has been implicated specifically in song learning. To further elucidate cellular mechanisms and circuitry involved in vocal learning, we used quantitative immunoblot analysis to determine if early song tutoring promotes within the AFP phosphorylation of calcium/calmodulin-dependent kinase II (CaMKII), a multifunctional kinase whose phosphorylation at threonine 286 is critical for many forms of neural plasticity and behavioral learning. We report that in young male zebra finches likely to have begun the process of song acquisition, brief tutoring by a familiar conspecific adult promotes a dramatic increase in levels of phosphorylated CaMKII (pCaMKII) in Area X, the striatal/pallidal component of the AFP. In contrast, pCaMKII levels in this region were not elevated if 1) the tutor did not sing, 2) the tutor sang but was visually isolated from the pupil, or 3) the tutor was an unfamiliar adult. In young males that had not previously heard any conspecific song, first exposure to a song tutor produced a more modest, but significant rise in pCaMKII levels. Young females (who do not develop song behavior) did not exhibit any effect of tutoring on pCaMKII levels in that portion of the basal ganglia that corresponds to Area X in males. These data are consistent with the hypothesis that Area X participates in encoding and/or attaching reward value to a representation of tutor song that is accessed later to guide motor learning.     

Social context-induced song variation affects female behavior and gene expression

Social cues modulate the performance of communicative behaviors in a range of species, including humans, and such changes can make the communication signal more salient. In songbirds, males use song to attract females, and song organization can differ depending on the audience to which a male sings. For example, male zebra finches (Taeniopygia guttata) change their songs in subtle ways when singing to a female (directed song) compared with when they sing in isolation (undirected song), and some of these changes depend on altered neural activity from a specialized forebrain-basal ganglia circuit, the anterior forebrain pathway (AFP). In particular, variable activity in the AFP during undirected song is thought to actively enable syllable variability, whereas the lower and less-variable AFP firing during directed singing is associated with more stereotyped song. Consequently, directed song has been suggested to reflect a “performance” state, and undirected song a form of vocal motor “exploration.” However, this hypothesis predicts that directed–undirected song differences, despite their subtlety, should matter to female zebra finches, which is a question that has not been investigated. We tested female preferences for this natural variation in song in a behavioral approach assay, and we found that both mated and socially naive females could discriminate between directed and undirected song—and strongly preferred directed song. These preferences, which appeared to reflect attention especially to aspects of song variability controlled by the AFP, were enhanced by experience, as they were strongest for mated females responding to their mate's directed songs. We then measured neural activity using expression of the immediate early gene product ZENK, and found that social context and song familiarity differentially modulated the number of ZENK-expressing cells in telencephalic auditory areas. Specifically, the number of ZENK-expressing cells in the caudomedial mesopallium (CMM) was most affected by whether a song was directed or undirected, whereas the caudomedial nidopallium (NCM) was most affected by whether a song was familiar or unfamiliar. Together these data demonstrate that females detect and prefer the features of directed song and suggest that high-level auditory areas including the CMM are involved in this social perception.     

Social Context–Induced Song Variation Affects Female Behavior and Gene Expression

Social cues modulate the performance of communicative behaviors in a range of species, including humans, and such changes can make the communication signal more salient. In songbirds, males use song to attract females, and song organization can differ depending on the audience to which a male sings. For example, male zebra finches (Taeniopygia guttata) change their songs in subtle ways when singing to a female (directed song) compared with when they sing in isolation (undirected song), and some of these changes depend on altered neural activity from a specialized forebrain-basal ganglia circuit, the anterior forebrain pathway (AFP). In particular, variable activity in the AFP during undirected song is thought to actively enable syllable variability, whereas the lower and less-variable AFP firing during directed singing is associated with more stereotyped song. Consequently, directed song has been suggested to reflect a “performance” state, and undirected song a form of vocal motor “exploration.” However, this hypothesis predicts that directed–undirected song differences, despite their subtlety, should matter to female zebra finches, which is a question that has not been investigated. We tested female preferences for this natural variation in song in a behavioral approach assay, and we found that both mated and socially naive females could discriminate between directed and undirected song—and strongly preferred directed song. These preferences, which appeared to reflect attention especially to aspects of song variability controlled by the AFP, were enhanced by experience, as they were strongest for mated females responding to their mate's directed songs. We then measured neural activity using expression of the immediate early gene product ZENK, and found that social context and song familiarity differentially modulated the number of ZENK-expressing cells in telencephalic auditory areas. Specifically, the number of ZENK-expressing cells in the caudomedial mesopallium (CMM) was most affected by whether a song was directed or undirected, whereas the caudomedial nidopallium (NCM) was most affected by whether a song was familiar or unfamiliar. Together these data demonstrate that females detect and prefer the features of directed song and suggest that high-level auditory areas including the CMM are involved in this social perception.     

Acute injections of brain-derived neurotrophic factor in a vocal premotor nucleus reversibly disrupt adult birdsong stability and trigger syllable deletion

Behavioral variability serves an essential role in motor learning by enabling sensory feedback to select those motor patterns that minimize error. Birds use auditory feedback to learn how to sing, and their songs lose variability and become highly stereotyped, or crystallized, at the end of a sensitive period for sensorimotor learning. The molecular cues that regulate song variability are not well understood. In other systems, neurotrophins, and brain-derived neurotrophic factor (BDNF) in particular, can mediate various forms of neural plasticity, including sensitive period neural circuit plasticity and activity-dependent synapse formation, and may also influence learning and memory. Here, we have tested the hypothesis that neurotrophin expression in the robust nucleus of the arcopallium (RA), the telencephalic output controlling song, regulates song variability. BDNF and its receptor trkB are expressed in RA, and BDNF expression in RA appears to be highest in juveniles, when song is most variable and plastic, and synapse density highest. Thus, song variability and synaptic connectivity could be enhanced by augmented expression of BDNF in RA. In support of this idea, we found that BDNF injections into the adult RA induced the re-expression of juvenile-like phenotypes, including song variability and an increased synaptic density in RA. Furthermore, BDNF treatment also induced vocal plasticity, characterized by syllable deletions and persistent changes to the song patterns. These results suggest that endogenous BDNF could be a molecular regulator of the song variability essential to vocal plasticity and, ultimately, to song learning.     

HVC microlesions do not destabilize the vocal patterns of adult male zebra finches with prior ablation of LMAN

The songs of adult male zebra finches (Taeniopygia guttata) arise by an integration of activity from two neural pathways that emanate from the telencephalic nucleus HVC (proper name). One pathway descends directly from HVC to the vocal premotor nucleus RA (the robust nucleus of the arcopallium) whereas a second pathway descends from HVC into a basal ganglia circuit (the anterior forebrain pathway, AFP) that also terminates in RA. Although HVC neurons that project directly to RA outnumber those that contribute to the AFP, both populations are distributed throughout HVC. Thus, partial ablation (microlesion) of HVC should damage both pathways in a proportional manner. We report here that bilateral HVC microlesions in adult male zebra finches produce an immediate loss of song stereotypy from which birds recover, in some cases within 3 days. The contribution of the AFP to the onset of song destabilization was tested by ablating the output nucleus of this circuit (LMAN, the lateral magnocellular nucleus of the anterior nidopallium) prior to bilateral HVC microlesions. Song stereotypy was largely unaffected. Together, our findings suggest that adult vocal production involves nonproportional integration of two streams of neural activity with opposing effects on song--HVC's direct projection to RA underlies production of stereotyped song whereas the AFP seems to facilitate vocal variation. However, the rapid recovery of song in birds with HVC microlesions alone suggests the presence of dynamic corrective mechanisms that favor vocal stereotypy.     

Changes in adult zebra finch song require a forebrain nucleus that is not necessary for song production

Male zebra finches normally crystallize song at approximately 90 days and do not show vocal plasticity as adults. However, changes to adult song do occur after unilateral tracheosyringeal (ts) nerve injury, which denervates one side of the vocal organ. We examined the effect of placing bilateral lesions in LMAN (a nucleus required for song development but not for song maintenance in adults) upon the song plasticity that is induced by ts nerve injury in adults. The songs of birds that received bilateral lesions within LMAN followed by right ts nerve injury silenced, on average, 0.25 syllables, and added 0.125 syllables (for an average turnover of 0.375 syllables), and changed neither the frequency with which individual syllables occurred within songs nor the motif types they used most often. In contrast, the songs of birds that received sham lesions followed by ts nerve injury lost, on average, 1.625 syllables, silenced 0.125 syllables, and added 0.75 syllables, turning over an average of 2.5 syllables. They also significantly changed both the frequency with which individual syllables were included in songs and the motif variants used. Thus, song plasticity induced in adult zebra finches with crystallized songs requires the presence of LMAN, a nucleus which had been thought to play a role in vocal production only during song learning. Although the changes to adult songs induced by nerve transection are more limited than those that arise during song development, the same circuitry appears to underlie both types of plasticity.     

Acute injections of brain‐derived neurotrophic factor in a vocal premotor nucleus reversibly disrupt adult birdsong stability and trigger syllable deletion

Behavioral variability serves an essential role in motor learning by enabling sensory feedback to select those motor patterns that minimize error. Birds use auditory feedback to learn how to sing, and their songs lose variability and become highly stereotyped, or crystallized, at the end of a sensitive period for sensorimotor learning. The molecular cues that regulate song variability are not well understood. In other systems, neurotrophins, and brain‐derived neurotrophic factor (BDNF) in particular, can mediate various forms of neural plasticity, including sensitive period neural circuit plasticity and activity‐dependent synapse formation, and may also influence learning and memory. Here, we have tested the hypothesis that neurotrophin expression in the robust nucleus of the arcopallium (RA), the telencephalic output controlling song, regulates song variability. BDNF and its receptor trkB are expressed in RA, and BDNF expression in RA appears to be highest in juveniles, when song is most variable and plastic, and synapse density highest. Thus, song variability and synaptic connectivity could be enhanced by augmented expression of BDNF in RA. In support of this idea, we found that BDNF injections into the adult RA induced the re‐expression of juvenile‐like phenotypes, including song variability and an increased synaptic density in RA. Furthermore, BDNF treatment also induced vocal plasticity, characterized by syllable deletions and persistent changes to the song patterns. These results suggest that endogenous BDNF could be a molecular regulator of the song variability essential to vocal plasticity and, ultimately, to song learning. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2005     

Evolution and plasticity: Divergence of song discrimination is faster in birds with innate song than in song learners in Neotropical passerine birds

Plasticity is often thought to accelerate trait evolution and speciation. For example, plasticity in birdsong may partially explain why clades of song learners are more diverse than related clades with innate song. This “song learning” hypothesis predicts that (1) differences in song traits evolve faster in song learners, and (2) behavioral discrimination against allopatric song (a proxy for premating reproductive isolation) evolves faster in song learners. We tested these predictions by analyzing acoustic traits and conducting playback experiments in allopatric Central American sister pairs of song learning oscines (N = 42) and nonlearning suboscines (N = 27). We found that nonlearners evolved mean acoustic differences slightly faster than did leaners, and that the mean evolutionary rate of song discrimination was 4.3 times faster in nonlearners than in learners. These unexpected results may be a consequence of significantly greater variability in song traits in song learners (by 54–79%) that requires song‐learning oscines to evolve greater absolute differences in song before achieving the same level of behavioral song discrimination as nonlearning suboscines. This points to “a downside of learning” for the evolution of species discrimination, and represents an important example of plasticity reducing the rate of evolution and diversification by increasing variability.     

Developmental patterns of NMDAR expression within the song system do not recur during adult vocal plasticity in zebra finches

All songbirds learn to sing during postnatal development but then display species differences in the capacity to learn song in adulthood. While the mechanisms that regulate avian vocal plasticity are not well characterized, one contributing factor may be the composition of N-methyl-D-aspartate receptors (NMDAR). Previous studies of an anterior forebrain pathway implicated in vocal plasticity revealed significant regulation of NMDAR subunit expression during the developmental sensitive period for song learning. Much less is known about the developmental regulation of NMDAR subunit expression in regions that participate more directly in motor aspects of song behavior. We show here that an increase in NR2A subunit mRNA and a decrease in NR2B subunit mRNA within the vocal motor pathway accompany song learning in zebra finches; however, manipulations that can alter the timing of song learning did not alter the course of these developmental changes. We also tested whether adult deafening, a treatment that provokes vocal change in songbirds that normally sing a stable song throughout adulthood, would render NMDAR subunit expression more similar to that observed developmentally. We report that NR2A and NR2B mRNA levels did not change within the anterior forebrain or vocal motor pathways after adult deafening, even after substantial changes in song structure. These results indicate that vocal plasticity does not require "juvenile patterns" of NMDAR gene expression in the avian song system.