Gene Regulation in Auditory Learning

描述（由申请人提供）：鸣禽是除了人类之外少数几个进化出声音学习的生物体之一，他们的研究有助于揭示声音交流和声音学习的神经基础。为了学会发出自己的歌声，并进行需要个人识别的社会行为，鸣禽需要处理并形成他们在生活中听到的歌曲的持久记忆。虽然在鸟鸣的运动方面已经取得了很大的进展，但我们对鸣禽用于分析和存储歌曲听觉信息的大脑区域和机制的理解仍然非常有限。对鸟鸣的听觉和感知方面的重要见解来自于以下发现：当鸟类听到歌声时，尾内侧新纹状体（NCM）中会发生zenk基因的显着诱导。zenk编码与神经元可塑性相关的转录调节因子，NCM是鸣禽大脑中枢听觉通路的一部分。分子、解剖、电生理和行为学研究表明，NCM在歌曲听觉加工中起着重要作用。特别是，证据已被发现在NCM的歌曲音节的听觉表示。这些研究还表明，在NCM的歌曲zenk诱导代表的基因调控级联反应，导致持久的神经元的变化，并可能形成和/或存储的歌曲听觉记忆的早期事件。 这项研究的目的是描述NCM的功能和解剖组织，并确定NCM中发生的基因组对歌曲的反应。具体目标是：1）确定作为NCM对歌曲反应的关键决定因素的刺激参数，并确定NCM中的音节表征是先天的还是依赖于经验的; 2）通过使用神经束示踪剂的小注射来确定NCM的解剖组织，以检查NCM内的功能子域具有不同连通性的程度;和3）通过a）鉴定NCM中歌曲调节的zenk靶基因，和B）确定zenk在NCM神经元对歌曲的长期习惯化中的作用，确定NCM中歌曲诱导的表达的作用。拟议研究的结果将为脊椎动物的大脑如何处理和存储行为相关的听觉信息提供基本见解，这将最终帮助我们了解与人类言语和语言障碍相关的大脑机制。

DESCRIPTION (provided by applicant): Songbirds are among the very few organisms that, besides humans, evolved vocal learning, and their study has helped uncover the neuronal basis of vocal communication and vocal learning. To learn to produce their own song and to perform social behaviors requiring individual recognition, songbirds need to process and to form long-lasting memories of the songs they hear in life. While there has been much progress with regards to motor aspects of birdsong, our understanding of the brain areas and mechanisms used by songbirds to analyze and store song auditory information is still very limited. Significant insight into auditory and perceptual aspects of birdsong has derived from the finding that a marked induction of the zenk gene occurs in the caudomedial neostriatum (NCM) when birds hear song. zenk encodes a transcriptional regulator linked to neuronal plasticity, and NCM is part of the central auditory pathway of the songbird brain. Evidence from molecular, anatomical, electrophysiological, and behavioral studies indicate that NCM plays a major role in song auditory processing. In particular, evidence has been uncovered for an auditory representation of song syllables in NCM. These studies also suggest that zenk induction by song in NCM represents an early event in a gene regulatory cascade that leads to long-lasting neuronal changes and possibly the formation and/or storage of song auditory memories. The objective of the proposed research is to characterize the functional and anatomical organization of NCM, and to determine the role of the genomic response to song that occurs in NCM. The specific aims are: 1) to identify stimulus parameters that are critical determinants of the NCM response to song and to determine whether the syllabic representation in NCM is innate or dependent on experience; 2) to determine the anatomical organization of NCM by using small injections of neuronal tract-tracers to examine the extent to which functional sub-domains within NCM have distinct connectivities; and 3) to determine the role of song-induced expression in NCM by a) identifying song regulated zenk target genes in NCM, and b) determining the role of zenk in the long-term habituation of NCM neurons to song. The outcomes of the proposed research will provide basic insights into how the brains of vertebrates process and store behaviorally relevant auditory information, which will eventually help us understand brain mechanisms associated with speech and language disorders in humans.