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学习发声的感觉和运动表征如何在鸣禽的基底神经节通路中传播和转化。鸣禽是探索类似于人类语音的声音-声音相互作用的重要模型，因为鸟鸣和语音需要听觉反馈，并涉及基底神经节通路。鸣禽的大脑包含一个明确的歌唱和歌曲学习回路，包括一个对听觉依赖的歌曲可塑性和感知至关重要的基底神经节通路。一个解剖专用和电生理可识别池的神经元在苍白球核HVC（HVCx神经元）是推定的来源，歌曲相关的听觉和运动活动的基底神经节通路。在这里，我们试图探索HVCx神经元如何在同一首歌的歌唱和听觉呈现过程中突触信号的基底神经节的目标。该提案的首要目标是在成年鸣禽中测试：1）抑制HVCX神经元是否会抑制基底神经节通路的输出，2）HVCx细胞在唱歌和歌曲播放期间传递时间相似的活动模式，以及3）改变的感觉反馈是否会破坏这种感觉运动相似性。这一建议的临床意义是双重的。首先，通过使用细胞内记录在麻醉鸟和细胞外记录从确定的神经元在自由行为的动物，拟议的实验将提供不寻常的洞察突触处理的行为显着模式的活动在基底神经节通路。其次，越来越多的研究，包括对遗传性运动障碍、口吃、抽动秽语综合征中的自发发声和帕金森氏病中的构音障碍的分析，指出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感觉运动加工的一般方面，同时揭示基底神经节通路中对声乐学习和维持很重要的声乐-声乐加工的专门方面。

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.