Neurophysiology of Sensorimotor Learning

描述（由申请人提供）：感觉反馈如何塑造习得行为的问题对于理解我们如何获得和失去技能至关重要。在雀形目鸟类，如斑胸草雀，歌曲的发展和成年歌曲的维持关键取决于听觉反馈，这些研究提供了深入了解在复杂的感觉运动行为的背景下学习的机制。最近的证据突出了令人惊讶的鸟鸣系统中的状态依赖性处理，表明在歌唱和听觉活动的表达的运动程序的组织是由胆碱能基底前脑（BF）的活动，包括对HVc神经元的影响。本计画利用细胞、系统与行为分析，探讨鸟鸣系统中行为状态在感觉运动学习中的角色。第一个实验将描述BF在调节歌唱中的作用。通过损伤或电刺激破坏BF后，将表现出歌唱行为的特征。BF操作将与设计用于操作听觉反馈的其他损伤相结合，测试BF是否有助于反馈介导的学习。歌唱过程中的单细胞记录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曲系统中传递的深入了解。第二个实验将阐明胆碱能活动的突触机制，操纵胆碱能环境和虚构的输出和听觉输入在体外脑片制备HVc。最后，将评估麻醉鸟类中记录的HVc细胞的胆碱能特性，以关联体内和体外结果。胆碱能活动长期以来一直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。本研究将验证胆碱能活动调节感觉运动学习的假说。积极的结果也可能有助于理解基底前脑退化和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.