Neurophysiology of Sensorimotor Learning

描述（由申请人提供）：感官反馈如何塑造习得行为的问题是理解我们如何获得和丢失技能的基础。在斑马草雀等雀鸟中，鸣叫的发展和成年鸣叫的维持严重依赖于听觉反馈，对这些反馈的研究有助于深入了解复杂感觉运动行为背景下的学习机制。最近的证据强调了鸟类鸣叫系统中令人惊讶的状态依赖处理，表明唱歌过程中运动程序的组织和听觉活动的表达是由胆碱能基底前脑（BF）的活动调节的，包括对HVc神经元的影响。利用细胞、系统和行为分析，本项目探讨了行为状态在鸟鸣系统中感觉运动学习中的作用。第一个实验将描述BF在调节鸣叫中的作用。歌唱行为将在BF受到损伤或电刺激后被表征。BF操作将与其他设计用于操纵听觉反馈的损伤相结合，测试BF是否有助于反馈介导的学习。歌唱过程中的单细胞录音将提供对包括听觉反馈信号在内的补偿反应如何在整个歌唱系统中传播的见解。第二个实验将阐明胆碱能活性的突触机制，在体外HVc脑切片制备中操纵胆碱能环境和有效输出和听觉输入。最后，将评估麻醉鸟类HVc细胞的胆碱能特性，并将体内和体外结果联系起来。长期以来，胆碱能活动与高度知觉注意状态有关，但其在感觉运动学习中的作用从未被广泛分析过。这个项目将检验胆碱能活动调节感觉运动学习的假设。积极的结果也可能有助于理解基底前脑退化与人类语言障碍之间的关系。

DESCRIPTION (provided by applicant): The question of how sensory feedback shapes learned behavior is fundamental to understanding how we acquire and loose skills. In passerine birds such as zebra finches, song development and adult song maintenance critically depend on auditory feedback, and the study of these gives insight into the mechanisms for learning in the context of complex sensorimotor behaviors. Recent evidence highlights surprising state-dependent processing in the birdsong system, showing that the organization of the motor program during singing and the expression of auditory activity is regulated by the activity of the cholinergic basal forebrain (BF), including effects on HVc neurons. Using cellular, systems, and behavioral analysis, this project explores the role of behavioral state in sensorimotor learning in the birdsong system. The first experiment will characterize the role of BF in regulating singing. Singing behavior will be characterized after disruption of BF by lesion or electrical stimulation. BF manipulations will be combined with other lesions designed to manipulate auditory feedback, testing if BF contributes to feedback mediated learning. Single cell recordings during singing will provide insight into how compensatory responses including auditory feedback signals are transmitted throughout the song system. The second experiment will elucidate the synaptic mechanisms of cholinergic activity, manipulating both the cholinergic milieu and fictive output and auditory input in an in vitro brain slice preparation of HVc. Finally, cholinergic properties of HVc cells recorded in anesthetized birds will be assessed to relate the in vivo and in vitro results. Cholinergic activity has long been associated with states of heightened perceptual attention, but its role in sensorimotor learning has never been extensively analyzed. This project will test the hypothesis that cholinergic activity regulates sensorimotor learning. Positive results may also contribute to an understanding of the relation between basal forebrain degeneration and language disturbances in humans.