Biochemical & synaptic substrates of learning

描述（由申请人提供）：拟议的研究调查突触可塑性的分子和解剖学基础，因为它们与年龄调节的感觉运动学习，鸟类鸣叫的发展的自然实例有关。鸟类的发声学习包括对特定感觉刺激的编码（鸣叫模型）和对发声运动模式的改进以模仿获得的模型。先前的研究表明，鸟鸣学习需要一种形式的NMDA受体（MDAR）依赖的突触可塑性在前脑的离散区域。这种可塑性通常依赖于钙调蛋白依赖性蛋白激酶II （CaMKII）的磷酸化（激活），最近的研究表明，在敏感学习期间短暂暴露于歌曲中会使前脑回路中的CaMKII磷酸化。此外，这种由歌曲引起的信号强度与有利于学习的刺激条件有关。定量免疫印迹（IB）将用于确定这种歌唱诱导的信号是否发生在其他歌唱区域，以及它是否伴随着CREB （cAMP反应元件结合蛋白）的磷酸化，CREB （cAMP反应元件结合蛋白）是一种参与突触强化稳定的事件。此外，声乐练习对这些细胞信号的单独和相互作用将被评估，免疫细胞化学将用于识别参与其表达的神经元亚群。颅间药理学操作将用于确定歌曲诱导的CaMKII激活对于正常的歌曲发育是否必要。最后一个实验的重点是突触重排，这一过程被认为是早期经验长期表征的基础。通过将鸣声学习的时间延迟到鸣声学习的正常敏感期结束后，我们将测试脊椎修剪与鸣声学习之间的关系。通过评估长期以来与神经可塑性有关的生化级联和突触变化是否也有助于鸟类的声乐学习，这项工作将阐明这些过程与自然发生的行为可塑性之间的关系。此外，这些研究将促进我们对构成声乐学习的认知过程如何在神经系统水平上分布和执行的理解。

DESCRIPTION (provided by applicant): The proposed studies investigate well-established molecular and anatomical substrates of synaptic plasticity as they relate to a natural instance of age-regulated sensorimotor learning, the development of avian song. Vocal learning in birds involves the encoding of a specific sensory stimulus (the song model) and a refinement of vocal motor patterns to emulate the acquired model. Previous studies suggest that birdsong learning entails a form of NMDA receptor (MDAR)-dependent synaptic plasticity within discrete regions of the anterior forebrain. Such plasticity frequently depends upon the phosphorylation (activation) of calcium calmodulin dependent protein kinase II (CaMKII), and recent work reveals that brief exposure to song during the sensitive learning period phosphorylates CaMKII within this forebrain circuit. Moreover, the strength of this song-induced signal relates to stimulus conditions that favor learning. Quantitative immunoblots (IB) will be used to determine if this song-induced signal occurs in other song regions, and if it is accompanied by phosphorylation of CREB (cAMP response element binding protein), an event involved in the stabilization of synaptic strengthening. Also, the separate and interactive effects of vocal practice on these cellular signals will be assessed, and immunocytochemistry will be used to identify the neuronal subpopulations involved in their expression. Intercranial pharmacological manipulations will be used to determine if the song-induced activation of CaMKII is necessary for normal song development. The final experiment focuses on synaptic rearrangement, a process believed to underlie long-term representations of early experience. By delaying the timing of song learning beyond the normal close of the sensitive period for song learning, the relationship between spine pruning and song learning will be tested. By evaluating whether biochemical cascades and synaptic changes long implicated in neural plasticity also contribute to avian vocal learning, the work will clarify how these processes relate to naturally-occurring behavioral plasticity. In addition, the studies will advance our understanding of how the cognitive processes that comprise vocal learning are distributed and executed at the neural systems level.