Learned vocal representations in avian basal ganglia

描述（由申请人提供）：我们的目标是在突触水平上分析习得发声的感觉和运动表征是如何在鸣禽的基底神经节通路中传播和转化的。鸣禽是探索类似于人类语言的听觉-声音相互作用的重要模型，因为鸟类的鸣叫和语言需要听觉反馈，并涉及基底神经节通路。鸣禽的大脑中有一个明确的歌唱和歌曲学习回路，包括一个基底神经节通路，这对依赖听力的歌曲可塑性和感知至关重要。在脑皮层核HVC （HVCx神经元）中，一个解剖学上专用的电生理上可识别的神经元池被认为是基底神经节通路中与歌曲相关的听觉和运动活动的来源。在这里，我们试图探索HVCx神经元如何在唱歌和听同一首歌的过程中突触地向其基底神经节目标发出信号。本研究的主要目标是在成年鸣禽中测试：1)抑制HVCX神经元是否解除了基底神经节通路的输出抑制，2)HVCX细胞在歌唱和歌曲回放过程中传递的活动模式在时间上是相似的，3)改变的感觉反馈是否破坏了这种感觉-运动的相似性。这一建议的临床意义是双重的。首先，通过使用麻醉鸟类的细胞内记录和自由行为动物中已识别神经元的细胞外记录，所提出的实验将为基底神经节通路中行为显著活动模式的突触处理提供不同寻常的见解。其次，越来越多的研究，包括对遗传性运动障碍、口吃、图雷特综合症的自发发声和帕金森氏症的构音障碍的分析，指出了基底神经节在人类语言中的重要作用。因此，本研究将阐明基底神经节中感觉运动加工的一般方面，同时揭示基底神经节中听觉-声乐加工的特殊方面，这些通路对声乐学习和维持至关重要。

DESCRIPTION (provided by applicant): Our objective is to analyze at the synaptic level how sensory and motor representations of learned vocalizations propagate and are transformed in basal ganglia pathways of the songbird. The songbird is an essential model for exploring auditory-vocal interactions akin to those underlying human speech, because birdsong and speech require auditory feedback and involve basal ganglia pathways. The songbird brain contains a well-defined circuit for singing and song learning, including a basal ganglia pathway essential to audition-dependent song plasticity and perception. An anatomically dedicated and electrophysiological identifiable pool of neurons in the pallial nucleus HVC (HVCx neurons) is the putative source of song-related auditory and motor activity in the basal ganglia pathway. Here we seek to explore how HVCx neurons synaptically signal their basal ganglia targets during singing and auditory presentation of the same song. This proposal's overarching goals are to test in adult songbirds whether: 1) inhibition onto HVCX neurons disinhibits the output of the basal ganglia pathway, 2) HVCx cells transmit temporally similar patterns of activity during singing and song playback, and 3) altered sensory feedback disrupts this sensory-motor similarity. The clinical significance of this proposal is two-fold. First, by using intracellular recordings in the anesthetized bird and extracellular recordings from identified neurons in the freely behaving animal, the proposed experiments will provide unusual insight into synaptic processing of behaviorally salient patterns of activity in basal ganglia pathways. Second, an increasing body of research including an analysis of heritable dyspraxias, stuttering, spontaneous vocalization in Tourette's syndrome and dysarthria in Parkinson's disease, points to an important role for the basal ganglia in human speech. Therefore, this research will illuminate generalized aspects of sensorimotor processing in the basal ganglia, while revealing specialized aspects of auditory-vocal processing in basal ganglia pathways important to vocal learning and maintenance.