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

FoxP在操作自学习中的作用是什么？

• 批准号: 376818398
• 负责人: Professor Dr. Björn Brembs
• 金额: --
• 依托单位: Institut für Zoologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/376818398?language=en
• 关键词: What; function; FoxP; operant; self

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.

Forkhead Box P2 (FOXP2) 转录因子是第一个被发现专门参与语音和语言发育的基因。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定形式的操作性条件作用（操作性自我学习）发挥这种参与作用。在操作性自学习中，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 基因家族已被确定在整个分类单元中发挥着重要作用。操作性自我学习的机制也被证明并不构成其他形式的学习的基础，例如操作性世界学习，允许对我们任何神经生物学操作的特异性进行非常严格的行为分析。在此应用中，我们提出了高度特异性、经过验证的遗传和生化工具以及严格的行为生理学的结合，以识别和表征果蝇果蝇中参与操作自学习的 FoxP 表达神经元和电路。为此，我们将产生转基因果蝇系，我们不仅可以一般性地操纵FoxP的表达，而且还可以操纵表达FoxP的神经元的活性。我们还将生成针对 FoxP 蛋白的单克隆抗体，不仅用于研究内源性 FoxP 表达模式，还用于验证和表征我们对 FoxP 表达的操作。然后，行为实验将提供有关哪些神经元中 FoxP 表达的哪些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，而且还与药物滥用、图雷特氏症或强迫症等精神疾病以及更广泛的运用障碍有关，因此操作性自学的基础科学对于临床治疗具有指导意义。也在这些领域进行研究。事实上，操作性自学正在被研究作为中风患者的一种治疗选择，目的是提高他们的活动能力。