Neural Analysis of Vocal Learning

描述(申请人提供)：基底节-皮质(BG)回路在正常运动行为(特别是顺序行为)和学习、动机和奖励以及许多神经精神障碍(包括精神分裂症、药物成瘾和帕金森氏症)中起着至关重要的作用。尽管这些通路很重要，但对它们的功能仍有很多需要了解的地方，部分原因是许多动物的回路及其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，用于深入了解BG的作用机制，因为它们相对简单的获得性发声行为--歌声--是由一组离散的大脑区域调节的，其中包括一个专门的BG回路。众所周知，这种前脑前通路(AFP)对发声学习和成人发声可塑性至关重要，并被认为是运动探索所必需的运动变异性和/或引导歌曲学习的适应性信号。然而，大多数关于AFP的体内神经生理学研究都集中在它的大脑皮质输出核‘LMan’上。因此，对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过环路时发生变化，人们知之甚少。在这项建议中，我们的目的是检验这一假设，即通过AFP对歌曲相关活动的编码有一个逐渐的转变，这可能对成人的可塑性和歌曲学习都是关键的。我们将首先从AFP的纹状体-苍白球部分的X区以及LMAN的多种细胞类型中记录清醒时成年斑雀在唱歌时的行为，并分析这两个区域的活动是如何共同变化的，以及它如何与歌唱有关(目标1)。然后，我们将通过药物抑制或损伤来操纵X区的活动，并评估对LMAN放电和SONG的影响(目标2)。这将检验目标1关于通过回路进行处理的想法，并应该揭示为什么X区和LMAN区的中断对歌曲可塑性有显著不同的影响。最后，我们将分析幼鸟在感觉运动学习过程中的X区和LMAN放电，此时SING的序列和音节稳定性仍然不同(目标3)。通过在学习完成之前研究这些回路，然后随着歌曲的结晶而跟踪神经的变化，我们应该对这个回路中的活动如何演变以及它与歌曲的准确性和稳定性之间的关系有了进一步的了解。这也将对AFP中的信号有助于可变性和/或指令的假设进行测试。对我们简单电路的分析有可能阐明BG电路如何发挥作用的非常一般的规则，无论是正常的还是在涉及这些结构的许多疾病中都是如此。

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.