鸣禽与人类发声器官及发声行为神经控制通路的比较

与人类语言学习或形成一样,鸣禽鸣唱也是一种发声学习行为,二者具有一定的相似性,例如发声学习过程均需听觉反馈的参与,幼年期具有更强的发声学习能力,可对复杂的声学结构和音节序列进行控制等。尽管鸣禽和人类的发声器官在结构上有很大差异,但二者发声的物理机制仍表现出很强的相似性。虽然相比于其他哺乳动物,鸣禽和人类的亲缘关系很远,但通过对比发声行为产生的基础通路——脑干先天发声控制通路,以及与发声学习相关的更高神经水平的发声运动和学习通路脑区位置、相互联系、功能及基因表达谱,提示鸣禽鸣唱和人类语言的神经控制具有一定的进化相似性。这些共同特征使得鸣禽成为了研究发声学习的理想模型。本文对鸣禽与人类的发声器官及发声行为的神经控制通路进行了比较,并对鸣禽模型在人类失语症治疗研究中潜在的应用前景进行了展望,以期为研究人类语言学习的神经机制及语言障碍的治疗带来理论参考和借鉴。     

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。     

鸟类的发声器官及其调控机制

鸟类是具有复杂声行为的动物,其拥有特殊的发声器官--鸣管.尽管鸣禽与非鸣禽的发声特性和发声器官解剖学差异较大,但是两者发声运动控制模式相似.文章综述了近年来鸟类鸣声研究的新进展,重点比较了鸣禽和非鸣禽发声器官的结构功能特点和发声特性调控的异同.作为一种动物模型,鸟类发声系统能为人类语言学习等研究提供借鉴.     

鸟类的发声系统和调控机制

鸟类是具有复杂声行为的动物,其拥有特殊的发声器官——鸣管。尽管鸣禽与非鸣禽的发声特性和发声器官解剖学差异较大,但是两者发声运动控制模式相似。文章综述了近年来鸟类呜声研究的新进展,重点比较了呜禽和非鸣禽发声器官的结构功能特点和发声特性调控的异同。作为一种动物模型,鸟类发声系统能为人类语言学习等研究提供借鉴。     

综述与专论: 鸣禽模型在语言学习中承担独特的生物学角色

鸣禽鸣唱与人类语言相似，是一种复杂的发声学习行为，并受脑中一组相互联系的神经核团调控。该组核团与人类发声控制相关脑区具有一定程度的结构同源性，并可能共享某些发声学习调控机制。因此，鸣禽成为研究发声学习神经机理的重要模式动物，不仅对鸟类语言学习，也可为揭示人类语言学习的神经过程和语言障碍的治疗提供重要参考借鉴。本文基于本课题组长期坚持的研究方向，较系统地概述了国内外鸣禽鸣唱行为研究的历史、重要发现和进展，及其为相关中枢神经系统疾病治疗带来的启示。     

中枢胆碱能系统投射支配鸣禽鸣唱控制系统并调控鸣唱行为

鸣禽因其独特的习得性鸣唱行为,成为了研究运动学习的理想模型。现已证实,鸣禽的鸣唱行为受前脑内的鸣唱控制系统直接调控。有证据显示,鸣唱控制系统内有胆碱能递质及其受体分布,其中发声运动核团接受来自基底前脑中枢胆碱能系统的胆碱能神经支配,其可通过胆碱能递质影响发声运动核团的神经活动,进而影响鸣唱行为。在哺乳动物中的研究证实,中枢胆碱能系统参与了对运动行为和运动学习神经过程的调控。了解中枢胆碱能系统对鸣禽鸣唱行为的调控作用,有助于更好地理解鸣禽鸣唱运动控制和鸣唱学习记忆的神经机制,并可从比较生理学的角度,为研究其它动物感觉运动和学习记忆的神经过程,乃至人类语言产生的神经过程提供重要参考。本文对迄今国内外在胆碱能递质对鸣禽发声运动核团作用受体的选择性及其对神经元活动影响的研究进展进行了综述,为揭示中枢胆碱能系统调控鸣禽鸣唱行为的神经机理提供有价值的线索。     

鸣禽锡嘴雀(Coccothraustes coccothraustes)发声中枢的定位研究

用常规组织学,HRP 逆行示踪,电生理等方法确定了鸣禽锡嘴雀控制发声的神经核团及这些核团的定位坐标值。锡嘴雀控制发声的神经通路由四级神经核团组成。位于端脑上纹状体腹侧的尾部区域(HVc)是控制鸣禽发声的高位中枢,它发出的神经纤维投射到端脑原纹状体腹内侧的粗核(RA),由 RA 又发出两束纤维,分別投射到中脑丘间核(ICo)和延脑的中间核(IM)。左右侧发声控制神经通路并非严格单侧性,每侧气管鸣管肌群分別受双侧发声中枢的交叉控制。中脑 ICo 在控制发声行为中具有相对独立性。各级发声核团的定位坐标值为,HVc∶p1.3,L/R2.4,H0.8;RA∶1.4,L/R3.2,H6.0;ICo∶p0.3,L/R2.6,H8.5:IM∶P3.1,L/R1.0,H∶7.8。     

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。     

成年鸣禽习鸣脑区的神经发生

成年鸣禽习鸣脑区可产生新的神经元。这些新生神经元沿神经胶质纤维迁移至鸣禽前脑高级发声控制与发声学习中枢,加入到原有的神经回路,参与发声学习记忆的感知与运动过程。这提示神经可塑性不仅适用于脑的发育,而且也是成年动物脑功能神经回路的一种正常过程。     

鸣禽控制发声核团和脑干听觉核团及神经通路的综合研究

采用辣根过氧化物酶顺、逆行标记方法对鸣禽鸟蜡嘴雀控制发声的神经核团、脑干听觉核团及神经通路,从外周至中枢逐级进行了追踪研究。结果表明：１．控制发声的神经核团及通路,前脑古纹状体腹内侧粗核是大脑控制发声的重要核团之一,它发出枕中脑后束经端脑前联合呈双侧支配延脑中间核,中间核又发出舌下神经经气管鸣管分支支配鸣肌,中间核同时也接受中脑背内侧核的支配,２．脑干听觉中枢及通路,中脑背外侧核是脑干较高级听觉中枢、初级中枢耳蜗核由角核和前庭外侧核组成,ＮＡ发出以对侧为主的纤维经外侧丘系可直接传入中脑背外侧核形成脑干听觉直接通路。     

Auditory-vocal cholinergic pathway in the songbird brain

Male zebra finches learn to imitate a tutor's song through auditory and motor learning. The two main song control nuclei in the zebra finch forebrain, the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA), receive cholinergic innervation from the ventral paleostriatum (VP) of the basal forebrain which may play a key role in song learning. By injecting neuroanatomical tracers, we found a topographically segregated pathway from nucleus ovoidalis (Ov) to VP that in turn projects in a topographic fashion to HVC and RA. Ov is a major relay in the main ascending auditory pathway. The results suggest that the cholinergic neurons in the VP responsible for song learning are regulated by auditory information from the Ov.     

A sensorimotor area in the songbird brain is required for production of vocalizations in the song learning period of development

Sensory feedback is essential for acquiring and maintaining complex motor behaviors, including birdsong. In zebra finches, auditory feedback reaches the song control circuits primarily through the nucleus interfacialis nidopalii (Nif), which provides excitatory input to HVC (proper name)—a premotor region essential for the production of learned vocalizations. Despite being one of the major inputs to the song control pathway, the role of Nif in generating vocalizations is not well understood. To address this, we transiently inactivated Nif in late juvenile zebra finches. Upon Nif inactivation (in both hemispheres or on one side only), birds went from singing stereotyped zebra finch song to uttering highly variable and unstructured vocalizations resembling sub‐song, an early juvenile song form driven by a basal ganglia circuit. Simultaneously inactivating Nif and LMAN (lateral magnocellular nucleus of the anterior nidopallium), the output nucleus of a basal ganglia circuit, inhibited song production altogether. These results suggest that Nif is required for generating the premotor drive for song. Permanent Nif lesions, in contrast, have only transient effects on vocal production, with song recovering within a day. The sensorimotor nucleus Nif thus produces a premotor drive to the motor pathway that is acutely required for generating learned vocalizations, but once permanently removed, the song system can compensate for its absence. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1213–1225, 2016     

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。     

Song, sexual selection, and a song control nucleus (HVc) in the brains of European sedge warblers

Female sedge warblers select males that have more complex songs as mates. This study tests two predictions concerning HVc, a telencephalic nucleus that is essential for song learning and production: first, that males with more complex songs will have a larger HVc, and second that males who pair successfully will have a larger HVc than unpaired males. Data on song composition and pairing status were collected from wild sedge warblers breeding in Hungary. We found significant positive correlations between three song attributes (repertoire size, song complexity, and song length) and the size of HVc. Males that paired successfully also had more complex songs (repertoire size and song complexity, though not song length) than males that did not. However, we find no direct evidence that males who paired successfully had a larger HVc than unpaired males. These findings are discussed in relation to the possible functions of HVc and also to current views on sexual selection and the evolution of the song control pathway.     

Developmental plasticity in neural circuits controlling birdsong: Sexual differentiation and the neural basis of learning

In many species of passerine songbirds, males learn their song during defined periods of life. Female song in often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the number of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior. © 1992 John Wiley & Sons, Inc.     

Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning.

In many species of passerine songbirds, males learn their song during defined periods of life. Female song is often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the numbers of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior.     

鸣禽栗鹀前脑鸣啭控制核团与性腺体积的相关性 *

用组织学技术和微机处理方法研究了春秋两季雄性成年鸣禽栗鹂前脑鸣啭相关核团体积与性腺体积之间的相关性。结果表明,与鸣啭控制直接相关的核团HVC、RA以及在鸣啭学习中具有重要作用的X区体积均随睾丸体积变化而发生显著的正相关性变化,而与发声无关的对照核团则没有这种相关性。     

The distribution of tyrosine hydroxylase in the canary brain: demonstration of a specific and sexually dimorphic catecholaminergic innervation of the telencephalic song control nuclei

Singing and the processing of auditory information related to song can be affected by experimental manipulations of catecholamine activity in the brain of zebra finches. We investigated, by immunocytochemistry in the brain of male and female canaries, the distribution of tyrosine hydroxylase (TH), the rate-limiting step in the synthesis of catecholamines. Fibers immunoreactive for TH (TH-ir) were particularly abundant in the lobus parolfactorius, the paleostriatum primitivum, and the nucleus septalis lateralis. A high density of TH-ir basket-like structures was observed in the caudomedial neostriatum, an area involved in song perception and recognition. In most males, a high density of TH-ir fibers outlined the telencephalic song control nuclei including the high vocal center, the nucleus robustus archistriatalis, the nucleus interfascialis, the lateral and medial parts of the magnocellular nucleus of the anterior neostriatum, and area X of the lobus parolfactorius. The higher density of fibers immunoreactive for TH in these nuclei, compared with the surrounding telencephalon, supports the notion that the morphological evolution of the song control nuclei was accompanied by a neurochemical specialization. This specific innervation of the song control regions was, in general, not found in females. The specific presence of high densities of TH-ir fibers in the song system of male canaries and the sex difference of this innervation provide anatomical evidence in support of the claim that dopamine and/or norepinephrine play important roles in the modulation of song learning and production.     

白腰文鸟发声行为的神经发育

本文研究了 5～ 15 0日龄雄性白腰文鸟 (Lonchurastriataswinhoei)不同年龄段的声谱变化以及这种变化的神经调制机制。结果如下 :(1)HVC、RA和AreaX三个发声核团的神经联系基本接近成年鸟的水平后 ,幼鸟才开始学习鸣叫 (约 45日龄 ) ;(2 )HVC、RA和AreaX达到成年核团体积时 (约 80日龄 ) ,幼鸟才具有成年雄鸟的鸣叫模式 ;(3)发声控制核团的发育与核团间的神经支配有关 ,而基本不受鸣唱行为的影响 ,HVC、RA和AreaX的最快增长时间段各不相同 ,三个核团随年龄增长而呈现体积增长的显著变化 (one wayANOVA ,P <0 0 5 ) ,但各核团在任意两个时间段的体积差异并不都显著。结果提示 :发声行为产生的时间和发展与发声控制核团的发育、核团间的神经联系有关 ,最终的体积发育程度受内在遗传力的作用 ,同时可能还受神经核团建立正常神经联系时间的影响     

Neurotensin and neurotensin receptor 1 mRNA expression in song‐control regions changes during development in male zebra finches

Learned vocalizations are important for communication in some vertebrate taxa. The neural circuitry for the learning and production of vocalizations is well known in songbirds, many of which learn songs initially during a critical period early in life. Dopamine is essential for motor learning, including song learning, and dopamine‐related measures change throughout development in song‐control regions such as HVC, the lateral magnocellular nucleus of the anterior nidopallium (LMAN), Area X, and the robust nucleus of the arcopallium (RA). In mammals, the neuropeptide neurotensin strongly interacts with dopamine signaling. This study investigated a potential role for the neurotensin system in song learning by examining how neurotensin (Nts) and neurotensin receptor 1 (Ntsr1) expression change throughout development. Nts and Ntsr1 mRNA expression was analyzed in song‐control regions of male zebra finches in four stages of the song learning process: pre‐subsong (25 days posthatch; dph), subsong (45 dph), plastic song (60 dph), and crystallized song (130 dph). Nts expression in LMAN during the subsong stage was lower compared to other time points. Ntsr1 expression was highest in HVC, Area X, and RA during the pre‐subsong stage. Opposite and complementary expression patterns for the two genes in song nuclei and across the whole brain suggest distinct roles for regions that produce and receive Nts. The expression changes at crucial time points for song development are similar to changes observed in dopamine studies and suggest Nts may be involved in the process of vocal learning. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 671–686, 2018