Neural Analysis of Vocal Learning

皮质-基底节(CBG)回路对正常的运动和强化学习至关重要，而且 相应地，是精神和神经病理的主要地点，包括精神分裂症和 上瘾。然而，由于其蜂窝和电路的复杂性，以及广泛的 它们控制的行为，许多关于这些神经信号之间的联系的基本问题 电路和行为仍然没有答案。在这方面，鸣禽提供了一个强有力的模式， 因为它们有一个专门的CBG环，即前脑前通路(AFP)，专门负责 定义明确的习得行为，歌声。最近对鸣禽的研究，包括我们从 在上一个授予周期中，提出了CBG电路的一个重要的新功能--有源产生 行为的可变性对学习很重要。与此一致的是，LMAN，‘皮质’流出 AFP的核心，承载着与歌曲相关的时间结构信号，以及逐个试验 围绕该信号的可变性。此外，神经和行为的变异性都可以显著地 当鸟儿处于社交的“表现”环境中时减少，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，以及它的基础 在歌曲网络中出现的模式，以及法新社的不同阶段是如何促成这些的 青少年和成年人的信号和歌唱，使用多个神经元的记录 结合甲胎蛋白的行为和药理作用。我们的首要目标是研究 环路中的第一个核，纹状体-苍白球X区，在单独的(无定向的)和 女性指导的歌唱，并将通过敏锐的 阻断LMAN递归输入或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活性对X区操作的响应， 以及它的丘脑目标DLm。最后，我们将测试可变性和模式化信号 在幼鸟学习的过程中，在LMAN中出现和进化，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的系统剖析不仅应该有助于 正常学习，但对这些回路的许多疾病，其症状通常包括 可变性很小或太多的。

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.