Neural Analysis of Vocal Learning

描述（由申请人提供）：基底神经节-皮质（BG）回路在正常运动行为（尤其是有序行为）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）中发挥着重要作用。尽管这些通路很重要，但它们的功能仍有待了解，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，提供了对BG作用机制的见解，因为它们相对简单的习得的声音行为，唱歌，是由一组离散的大脑区域调节的，其中包括一个专门的BG电路。众所周知，这种“前前脑通路”（AFP）对声乐学习和成人声乐可塑性至关重要，并且已经表明它有助于运动探索和/或指导歌曲学习的适应性信号所必需的运动变异性。然而，大多数AFP的体内神经生理学研究都集中在其pallial输出核“LMAN”上。因此，对于行为端正的鸟类回路的其他组成部分，以及歌唱过程中的神经放电是否以及如何在回路中发生变化，我们所知相对较少。在这一建议中，我们的目标是测试假设，即通过AFP编码与歌曲相关的活动的逐渐转变，这可能对成人可塑性和歌曲学习都至关重要。我们将首先记录下成年斑胸草雀在歌唱过程中，AFP的纹状体-苍白质部分X区以及LMAN的多种细胞类型，并分析这两个区域的活动是如何共同变化的，以及它与歌唱的关系（目的1）。然后，我们将通过药物抑制或病变来控制X区的活动，并评估对LMAN放电和歌唱的影响（目的2）。这将测试目标1中关于通过电路处理的想法，也应该阐明为什么X区和LMAN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，此时鸣声的顺序和音节稳定性仍然不同（Aim 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该回路中的活动是如何演变的，以及它与歌曲的准确性和稳定性之间的关系。这也将为AFP中的信号有助于变异和/或指示的假设提供检验。对我们的简单电路的分析有可能阐明关于BG电路如何正常运作的非常一般的规则，以及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.