NMDA受体与鸣禽鸣唱学习记忆

N-2-甲基-D-天冬氨酸(N-methy-2-D-asparticacid,NMDA)受体,是一种分布在突触后膜上的离子通道蛋白,受突触电压和神经递质(如谷氨酸、甘氨酸、NMDA等)的双重调控,是参与学习与记忆过程的关键物质.鸣禽的鸣唱是一种习得性行为,是在特定的学习敏感期依赖听觉经验完成的.对近年来鸣禽NMDA受体与鸣禽鸣唱学习的研究进展进行了综述.     

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。     

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.     

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。     

鸣禽前脑听觉和鸣唱系统zenk基因的诱导表达

鸣曲和鸣唱行为可以诱导鸣禽前脑不同区域的zenk基因表达.鸣禽听到同类鸣曲时在听觉系统会出现zenk表达,并在致聋后这种诱导消失.而鸣禽鸣唱时,在鸣唱系统同样有zenk基因的表达,且不依赖于听觉反馈,因为致聋鸟只要发声就可以诱导表达.大量的研究表明,zenk基因在听区的诱导表达不仅可对同类鸣曲进行识别,而且在教习曲模板的记忆方面发挥重要作用.鸣唱系统zenk基因诱导表达则主要与鸣曲的产生与维持有关.zenk基因在两个系统中的诱导表达将听觉感知与鸣唱运动紧密联系起来.     

多巴胺系统调控鸣禽鸣唱相关神经核团及鸣唱行为

鸣禽的鸣唱与人类的语言产生相似,是一种复杂的习得性行为.因此,鸣禽可以作为研究人类语言学习与产生的重要模式动物.鸣禽鸣唱受到相互联系的鸣唱控制核团调控.多巴胺作为脑内重要的神经递质,参与调控哺乳动物多种活动.多巴胺及其受体在鸣禽鸣唱相关神经核团大量分布.近期研究表明,多巴胺通过调控鸣唱相关核团,促进鸣禽幼年期鸣曲学习、成年期鸣曲保持以及求偶性鸣唱的产生.本文结合本课题组的研究工作,对近年鸣禽多巴胺系统调控鸣唱相关神经核团及鸣唱行为的研究进展进行了综述,并提出了多巴胺信号调控鸣禽鸣唱学习行为的潜在机制.     

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.     

致聋对鸣禽鸣唱行为的影响

鸣禽的鸣啭系统已是当今研究学习和记忆的重要模型。鸣禽的鸣啭学习包括2个阶段：感觉学习期和感觉-运动学习期,以及鸣唱运动和鸣唱学习2条通路。鸣禽的鸣唱行为依赖于听觉反馈系统,现已经证明致聋会使鸣曲结构发生变化,主要对近年来在致聋与鸣唱行为的影响及一些电生理变化研究方面进行介绍。     

儿茶酚胺能神经元与鸣禽鸣唱行为和听觉信息处理

鸣禽脑部的一些鸣唱核团与听觉核团接受来自中脑儿茶酚胺(catecholamine,CA)能神经元发出的纤维投射,并且存在多种儿茶酚胺类受体的表达。研究发现在不同的鸣唱环境下,中脑儿茶酚胺能神经元活性及其支配靶区即早基因的表达水平均存在显著差异。表明中脑儿茶酚胺能神经元在调节鸣唱行为和听觉信息处理等方面发挥重要作用。介绍了近年来有关儿茶酚胺能神经元活动与鸣唱行为和听觉信息处理的研究进展。     

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.     

A Lightweight,Headphones-based System for Manipulating Auditory Feedback in Songbirds

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and sensorimotor plasticity¹. Consistent sensory perturbations result in compensatory changes in motor output, reflecting changes in feedforward motor control that reduce the experienced feedback error. By quantifying how different sensory feedback errors affect human behavior, prior studies have explored how visual signals are used to recalibrate arm movements^2,3 and auditory feedback is used to modify speech production^4-7. The strength of this approach rests on the ability to mimic naturalistic errors in behavior, allowing the experimenter to observe how experienced errors in production are used to recalibrate motor output.Songbirds provide an excellent animal model for investigating the neural basis of sensorimotor control and plasticity^8,9. The songbird brain provides a well-defined circuit in which the areas necessary for song learning are spatially separated from those required for song production, and neural recording and lesion studies have made significant advances in understanding how different brain areas contribute to vocal behavior^9-12. However, the lack of a naturalistic error-correction paradigm - in which a known acoustic parameter is perturbed by the experimenter and then corrected by the songbird - has made it difficult to understand the computations underlying vocal learning or how different elements of the neural circuit contribute to the correction of vocal errors¹³.The technique described here gives the experimenter precise control over auditory feedback errors in singing birds, allowing the introduction of arbitrary sensory errors that can be used to drive vocal learning. Online sound-processing equipment is used to introduce a known perturbation to the acoustics of song, and a miniaturized headphones apparatus is used to replace a songbird''s natural auditory feedback with the perturbed signal in real time. We have used this paradigm to perturb the fundamental frequency (pitch) of auditory feedback in adult songbirds, providing the first demonstration that adult birds maintain vocal performance using error correction¹⁴. The present protocol can be used to implement a wide range of sensory feedback perturbations (including but not limited to pitch shifts) to investigate the computational and neurophysiological basis of vocal learning.     

Vocal Learning in Songbirds and Humans: A Retrospective in Honor of Peter Marler

Peter Marler made a number of significant contributions to the field of ethology, particularly in the area of animal communication. His research on birdsong learning gave rise to a thriving subfield. An important tenet of this growing subfield is that parallels between birdsong and human speech make songbirds valuable as models in comparative and translational research, particularly in the case of vocal learning and development. Decades ago, Marler pointed out several phenomena common to the processes of vocal development in songbirds and humans—including a dependence on early acoustic experience, sensitive periods, predispositions, auditory feedback, intrinsic reinforcement, and a progression through distinct developmental stages—and he advocated for the value of comparative study in this domain. We review Marler's original comparisons between birdsong and speech ontogeny and summarize subsequent progress in research into these and other parallels. We also revisit Marler's arguments in support of the comparative study of vocal development in the context of its widely recognized value today.     

Feedback Valence Affects Auditory Perceptual Learning Independently of Feedback Probability

Previous studies have suggested that negative feedback is more effective in driving learning than positive feedback. We investigated the effect on learning of providing varying amounts of negative and positive feedback while listeners attempted to discriminate between three identical tones; an impossible task that nevertheless produces robust learning. Four feedback conditions were compared during training: 90% positive feedback or 10% negative feedback informed the participants that they were doing equally well, while 10% positive or 90% negative feedback informed them they were doing equally badly. In all conditions the feedback was random in relation to the listeners’ responses (because the task was to discriminate three identical tones), yet both the valence (negative vs. positive) and the probability of feedback (10% vs. 90%) affected learning. Feedback that informed listeners they were doing badly resulted in better post-training performance than feedback that informed them they were doing well, independent of valence. In addition, positive feedback during training resulted in better post-training performance than negative feedback, but only positive feedback indicating listeners were doing badly on the task resulted in learning. As we have previously speculated, feedback that better reflected the difficulty of the task was more effective in driving learning than feedback that suggested performance was better than it should have been given perceived task difficulty. But contrary to expectations, positive feedback was more effective than negative feedback in driving learning. Feedback thus had two separable effects on learning: feedback valence affected motivation on a subjectively difficult task, and learning occurred only when feedback probability reflected the subjective difficulty. To optimize learning, training programs need to take into consideration both feedback valence and probability.     

Attentional Demands Influence Vocal Compensations to Pitch Errors Heard in Auditory Feedback

Auditory feedback is required to maintain fluent speech. At present, it is unclear how attention modulates auditory feedback processing during ongoing speech. In this event-related potential (ERP) study, participants vocalized/a/, while they heard their vocal pitch suddenly shifted downward a ½ semitone in both single and dual-task conditions. During the single-task condition participants passively viewed a visual stream for cues to start and stop vocalizing. In the dual-task condition, participants vocalized while they identified target stimuli in a visual stream of letters. The presentation rate of the visual stimuli was manipulated in the dual-task condition in order to produce a low, intermediate, and high attentional load. Visual target identification accuracy was lowest in the high attentional load condition, indicating that attentional load was successfully manipulated. Results further showed that participants who were exposed to the single-task condition, prior to the dual-task condition, produced larger vocal compensations during the single-task condition. Thus, when participants’ attention was divided, less attention was available for the monitoring of their auditory feedback, resulting in smaller compensatory vocal responses. However, P1-N1-P2 ERP responses were not affected by divided attention, suggesting that the effect of attentional load was not on the auditory processing of pitch altered feedback, but instead it interfered with the integration of auditory and motor information, or motor control itself.     

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。     

Female Social Feedback Reveals Non-imitative Mechanisms of Vocal Learning in Zebra Finches

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Hemispheric Asymmetry in New Neurons in Adulthood Is Associated with Vocal Learning and Auditory Memory

Many brain regions exhibit lateral differences in structure and function, and also incorporate new neurons in adulthood, thought to function in learning and in the formation of new memories. However, the contribution of new neurons to hemispheric differences in processing is unknown. The present study combines cellular, behavioral, and physiological methods to address whether 1) new neuron incorporation differs between the brain hemispheres, and 2) the degree to which hemispheric lateralization of new neurons correlates with behavioral and physiological measures of learning and memory. The songbird provides a model system for assessing the contribution of new neurons to hemispheric specialization because songbird brain areas for vocal processing are functionally lateralized and receive a continuous influx of new neurons in adulthood. In adult male zebra finches, we quantified new neurons in the caudomedial nidopallium (NCM), a forebrain area involved in discrimination and memory for the complex vocalizations of individual conspecifics. We assessed song learning and recorded neural responses to song in NCM. We found significantly more new neurons labeled in left than in right NCM; moreover, the degree of asymmetry in new neuron numbers was correlated with the quality of song learning and strength of neuronal memory for recently heard songs. In birds with experimentally impaired song quality, the hemispheric difference in new neurons was diminished. These results suggest that new neurons may contribute to an allocation of function between the hemispheres that underlies the learning and processing of complex signals.     

Song Learning, Early Nutrition and Sexual Selection in Songbirds

SYNOPSIS. The developmental processes through which songbirdsacquire their species—typical songs have been well—studiedfrom a proximate perspective, but less attention has been givento the ultimate question of why birds learn to sing. We presenta new hypothesis for the adaptive significance of song learningin songbirds, suggesting that this specialized form of vocaldevelopment provides an indicator mechanism by which femalescan accurately assess the quality of potential mates. This hypothesisexpands on the established idea that song can provide an indicatorof male quality, but it explicitly links the variation in songexpression that females use to choose mates to the developmentalprocesses through which song is acquired. How well a male sings—reflectedin repertoire size or in other learned features of a male'ssinging behavior—provides an honest indicator of qualitybecause the timing of song learning and, more importantly, thetiming of the development of brain structures mediating learningcorresponds to a period in development during which young songbirdsare most likely to undergo nutritional stress. This correspondencemeans that song learning can provide a sensitive indicator ofearly developmental history in general, which in turn reflectsvarious aspects of the phenotypic and genotypic quality of apotential mate.     

Representation of Early Sensory Experience in the Adult Auditory Midbrain: Implications for Vocal Learning

Vocal learning in songbirds and humans occurs by imitation of adult vocalizations. In both groups, vocal learning includes a perceptual phase during which juveniles birds and infants memorize adult vocalizations. Despite intensive research, the neural mechanisms supporting this auditory memory are still poorly understood. The present functional MRI study demonstrates that in adult zebra finches, the right auditory midbrain nucleus responds selectively to the copied vocalizations. The selective signal is distinct from selectivity for the bird''s own song and does not simply reflect acoustic differences between the stimuli. Furthermore, the amplitude of the selective signal is positively correlated with the strength of vocal learning, measured by the amount of song that experimental birds copied from the adult model. These results indicate that early sensory experience can generate a long-lasting memory trace in the auditory midbrain of songbirds that may support song learning.