Neural Analysis of Vocal Learning

皮质-基底神经节（CBG）回路对于正常的运动和强化学习至关重要， 因此是精神和神经病理学的主要部位，包括精神分裂症， 上瘾然而，由于它们的蜂窝和电路复杂性， 他们控制的行为，许多关于这些神经信号之间联系的基本问题， 电路和行为仍然没有答案。鸣禽在这方面提供了一个强有力的模型， 因为他们有一个专门的CBG回路，前前脑通路（AFP），专门用于 明确的习得行为宋最近对鸣禽的研究，包括我们自己的工作， 上一个授权周期，提出了CBG电路的一个重要的新功能，即主动生成 行为变异性对学习很重要。与此一致，LMAN，“皮质”流出 AFP的核，携带与歌曲相关的时间结构信号， 信号周围的变化。此外，神经和行为的变异性可以明显地 当鸟类处于社会“表现”环境中时，可能会减少，可能是对中脑的反应。 多巴胺（DA）释放。我们现在要问的是，神经变异性是如何发生的，在哪里发生的， 模式出现在歌曲网络，以及如何不同阶段的AFP有助于这些 信号和歌曲在青少年和成年人，使用记录的多个神经元， 结合AFP的行为和药理学操作。我们的首要目标是研究 回路中的第一个核，纹状体-苍白球X区，在单独（“无定向”）和 女性主导的歌唱，并将测试可能的来源，上下文依赖的变化，通过剧烈 阻断LMAN重复输入或DA受体。我们的第二个目标将进一步检验 AFP的不同阶段，通过检查LMAN活动对X区域操纵的反应， 以及丘脑靶点DLM的影响。最后，我们将测试可变性和模式信号 在幼鸟学习过程中LMAN的出现和进化，以及它们如何对社会线索做出反应。 对该系统中可能的电路功能进行系统的剖析，不仅可以阐明 正常的学习，但对这些电路的许多疾病，其症状往往包括太 太少或太多的变化。

Cortical-basal ganglia (CBG) circuits are critical for normal motor and reinforcement learning, and accordingly are a major site of psychiatric and neurological pathology, including schizophrenia and addictions. However, because of their cellular and circuit complexity, and the broad suite of behaviors they control, many basic questions about the link between neural signals in these circuits and behavior remain unanswered. Songbirds provide a powerful model in this regard, because they have a specialized CBG loop, the anterior forebrain pathway (AFP), devoted to a well-defined learned behavior, song. Recent studies in songbirds, including our own work from the last grant cycle, have suggested an important new function for CBG circuits, the active generation of behavioral variability important for learning. Consistent with this, LMAN, the 'cortical' outflow nucleus of the AFP, carries both a temporally structured signal related to song, and trial-by-trial variability around that signal. Moreover, both neural and behavioral variability can markedly decrease when birds are in a social, 'performance' context, possibly in response to midbrain dopamine (DA) release. We will now ask how and where neural variability and its underlying pattern emerge in the song network, and how the different stages of the AFP contribute to these signals and to song in both juveniles and adults, using recordings of multiple neurons in combination with behavioral and pharmacological manipulations of the AFP. Our first aim will study the first nucleus in the circuit, the striato-pallidal Area X , during both alone ('undirected') and female-directed singing, and will test possible sources of context-dependent variation by acutely blocking LMAN recurrent inputs or DA receptors. Our second aim will further test the importance of different stages of the AFP by examining LMAN activity in response to manipulations of Area X, and of its thalamic target DLM. Finally, we will test how both variability and patterned signals emerge and evolve in LMAN during learning in juvenile birds, and how they respond to social cues. The systematic dissection of circuit function possible in this system should shed light not only on normal learning, but on the many diseases of these circuits, whose symptoms often include too little or too much variability.