What is the function of FoxP in operant self-learning?

叉头盒P2（FOXP 2）转录因子是第一个被发现的基因，专门参与语音和语言的发展。最近对鸟类、小鼠和果蝇的研究表明，该基因通过其保守功能以一种特殊的操作性条件反射形式发挥这种作用：操作性自我学习。在操作性自我学习中，主体了解自己行为的结果，并相应地修改行为。这种最近描述的学习形式背后的神经生物学在很大程度上是未知的，只有蛋白激酶C和FoxP基因家族在分类群中被确定为关键参与。操作性自我学习的基础机制也被证明不是其他学习形式的基础，比如操作性世界学习，这使得我们可以对任何神经生物学操作的特异性进行非常严格的行为分析。在这个应用程序中，我们提出了一个高度具体的，验证的遗传和生化工具和严格的行为生理学相结合，识别和表征的FoxP表达神经元和电路参与操作性自我学习的果蝇。为此，我们将产生转基因果蝇品系，我们将不仅操纵FoxP的表达，而且操纵FoxP表达神经元的活性。我们还将产生针对FoxP蛋白的单克隆抗体，不仅研究内源性FoxP表达模式，而且验证和表征我们对FoxP表达的操作。然后，行为实验将提供关于哪些神经元中FoxP表达的操作或哪些神经元的激活/失活对操作性自我学习（而不是操作性世界学习）有特定影响的信息。这项果蝇研究的结果将为我们提供一种新形式的行为学习（操作性自我学习）的机制见解，这是人类言语和语言习得的重要神经生物学基础之一。由于这种形式的学习不仅与言语和语言障碍有关，而且与精神疾病如药物滥用、妥瑞氏症或强迫症以及更广泛的运动障碍有关，因此操作性自我学习的基础科学对这些领域的临床研究也具有指导意义。事实上，操作性自我学习正在被研究作为中风患者的一种治疗选择，目的是增加他们的流动性。

The Forkhead Box P2 (FOXP2) transcription factor is the first gene discovered to be specifically involved in the development of speech and language. Recent studies in birds, mice and fruit flies have shown that the gene exerts this involvement via its conserved function in a particular form of operant conditioning: operant self-learning. In operant self-learning, the subject learns about the outcomes of its own behavior and modifies the behavior accordingly. The neurobiology underlying this recently described form of learning is largely unknown, only Protein Kinase C and the FoxP gene family have been identified across taxa to be critically involved. The mechanism underlying operant self-learning has also been shown not to underlie other forms of learning, such as operant world-learning, allowing for a very rigorous behavioral analysis of the specificity of any of our neurobiological manipulations. In this application, we propose a combination of highly specific, validated genetic and biochemical tools and rigorous behavioral physiology, to identify and characterize the FoxP expressing neurons and circuits involved in operant self-learning in the fruit fly Drosophila. To this end, we will generate transgenic fly lines with which we will manipulate not only the expression of FoxP generally, but also the activity of FoxP expressing neurons. We will also generate monoclonal antibodies against the FoxP protein not only to study endogenous FoxP expression patterns, but also to validate and characterize our manipulations of FoxP expression. Behavioral experiments will then provide the information about which manipulation of FoxP expression in which neurons or the activation/inactivation of which neurons had a specific effect on operant self-learning (and not operant world-learning). The results of this research in the fruit fly will provide us with mechanistic insights into a novel form of behavioral learning (operant self-learning) which is one of the essential neurobiological underpinnings of speech and language acquisition in humans. As this form of learning is associated not only with speech and language disorders, but also with psychiatric disorders such as substance abuse, Tourette's or compulsive disorders, as well as with dyspraxias more broadly, the basic science on operant self-learning is instructive for clinical research in these areas as well. In fact, operant self-learning is being researched as one treatment option for stroke patients, with the aim to increase their mobility.