Gene Regulation in Auditory Learning

描述（由申请人提供）：鸣禽是除人类之外极少数进化出声音学习的生物之一，它们的研究有助于揭示声音交流和声音学习的神经元基础。为了学会发出自己的歌声，并完成需要个体识别的社会行为，鸣禽需要处理并形成它们在生活中听到的歌曲的持久记忆。虽然在鸟类鸣叫的运动方面已经取得了很大的进展，但我们对鸣禽分析和存储鸣叫听觉信息的大脑区域和机制的理解仍然非常有限。当鸟类听到歌声时，尾状新纹状体（NCM）中会出现zenk基因的显著诱导，这一发现对鸟类鸣叫的听觉和感知方面产生了重要的见解。zenk编码一种与神经元可塑性相关的转录调节因子，而NCM是鸣禽大脑中央听觉通路的一部分。来自分子、解剖、电生理和行为研究的证据表明，NCM在歌曲听觉加工中起着重要作用。特别是，已经发现了NCM中歌曲音节的听觉表征的证据。这些研究还表明，歌曲在NCM中诱导zenk代表了基因调控级联中的一个早期事件，该级联可导致持久的神经元变化，并可能形成和/或储存歌曲听觉记忆。

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.