Neural Analysis of Vocal Learning

描述（由申请人提供）：基底神经节-皮质（BG）回路与正常运动行为（特别是序列行为）和学习、动机和奖励以及许多神经精神疾病（包括精神分裂症、药物成瘾和帕金森病）密切相关。尽管这些通路很重要，但关于它们的功能还有很多东西需要了解，部分原因是许多动物的回路和它们控制的行为都很复杂。鸣禽提供了一个潜在的强大的小动物模型，提供BG行动机制的见解，因为他们相对简单的学习声乐行为，歌曲，是由一组离散的大脑区域，包括一个专门的BG电路介导。这是公认的，这“前脑通路”（AFP）是至关重要的声乐学习和成人声乐可塑性，它已被建议，它有助于运动变异性必要的运动探索和/或自适应信号，以指导歌曲学习。然而，大多数在体AFP的神经生理学研究都集中在其苍白球输出核'LMAN'。因此，对于鸟类行为回路的其他组成部分，以及在歌唱过程中神经放电是否以及如何在穿越回路时发生变化，我们知之甚少。在这个建议中，我们的目标是测试的假设，有一个渐进的转变编码的歌曲相关的活动，通过AFP可能是至关重要的成人可塑性和歌曲学习。我们将通过首先记录AFP，X区，以及LMAN中的纹状体苍白球部分的多种细胞类型来实现这一点，在清醒时，行为成年斑胸草雀在唱歌时，并分析这两个区域的活动如何共同变化，以及它如何与歌曲相关（目的1）。然后，我们将操纵X区的活动，无论是药物抑制还是损伤，并评估对LMAN放电和歌曲的影响（目标2）。这将测试目标1中关于通过回路进行处理的想法，也应该阐明为什么X区域和LMAN的中断对歌曲可塑性有着惊人的不同影响。最后，我们将分析在感觉运动学习过程中，当歌曲的顺序和音节稳定性仍然变化时，幼鸟的X区和LMAN放电（目的3）。通过在学习完成之前研究这些回路，然后跟踪歌曲结晶时的神经变化，我们应该进一步了解这个回路中的活动如何演变，以及它如何与歌曲的准确性和稳定性相关。这也将提供对AFP中的信号贡献可变性和/或指令的假设的检验。对我们简单回路的分析有可能阐明BG回路如何发挥作用的一般规则，无论是在正常情况下还是在涉及这些结构的许多疾病中。

DESCRIPTION (provided by applicant): Basal ganglia-cortical (BG) circuits are critically involved in normal motor behavior (especially sequenced behavior) and learning, in motivation and reward, and in numerous neuropsychiatric disorders, including schizophrenia, drug addictions, and Parkinson's disease. Despite the importance of these pathways, much remains to be learned about their function, in part because of the complexity in many animals both of the circuits and of the behaviors they control. Songbirds provide a potentially powerful small animal model for providing insights into mechanisms of BG action, because their relatively simple learned vocal behavior, song, is mediated by a discrete set of brain areas that includes a specialized BG circuit. It is well-established that this 'anterior forebrain pathway' (AFP) is critical for vocal learning and adult vocal plasticity, and it has been suggested that it contributes motor variability necessary for motor exploration and/or adaptive signals to guide song learning. However, most in vivo neurophysiological studies of the AFP have focused on its pallial output nucleus 'LMAN'. Thus, relatively little is known about other components of the circuit in behaving birds and about whether and how neural firing during singing changes as it traverses the loop. In this proposal we aim to test the hypothesis that there is a gradual transformation of the encoding of song- related activity through the AFP that is likely to be critical both to adult plasticity and to song learning. We will accomplish this by first recording from multiple cell types in the striato-pallidal portion of the AFP, Area X, as well as from LMAN, in awake, behaving adult zebra finches during singing, and analyzing how the activity in these two regions co-varies, and how it relates to song (Aim 1). We will then manipulate activity in Area X, either with pharmacological inhibition or with lesions, and assess the effects on LMAN firing and on song (Aim 2). This will test ideas from Aim 1 about processing through the circuit, and should also shed light on why disruptions of Area X and LMAN have strikingly different effects on song plasticity. Finally, we will analyze Area X and LMAN firing in young birds in the process of sensorimotor learning, when song still varies in its sequence and syllable stability (Aim 3). By studying these circuits before learning is complete and then following the neural changes as song is crystallized, we should gain further insights into how activity evolves in this circuit and how it relates to the accuracy and stability of song. This will also provide tests of the hypotheses that signals in the AFP contribute variability and/or instruction. Analyses of our simple circuit have the potential to elucidate very general rules about how BG circuits function, both normally and in the many diseases in which these structures are involved.