Adf1 transcription in behaviorial & synaptic plasticity

描述(申请人提供)：我们正在应用果蝇模型系统的规模经济来识别与可塑性有关的基因。我们已经开发了一种巴甫洛夫式的嗅觉学习测试，它显示了动物王国中用于联想学习的各种行为特性。到目前为止，已发现的大多数基因都被证明参与了脊椎动物和无脊椎动物模型系统中各种形式的行为或突触可塑性。我们已经确定了一个基因，adf1，它在成人长期记忆的形成(行为可塑性)和幼虫神经肌肉接头的突触形成(发育可塑性)中起着明显的作用。Adf1基因编码一种转录因子，没有其他已知的生物学功能。我们假设ADF1是活性依赖突触可塑性的分子成分。我们建议通过进一步的实验来确定ADF1是否与其他参与突触可塑性的分子成分相互作用，如cAMP(PKA)或Jun Kinase(JNK)信号通路、CREB转录途径或细胞黏附分子，以及(Ii)观察ADF1依赖的基因在发育或行为过程中的表达。最终，这些知识将有助于揭示各种形式的认知功能障碍，这些功能障碍是由遗传、疾病、伤害或年龄引起的。由于大脑是一个高度可塑性的器官，我们最终将能够通过干预行为、药物甚至基因疗法，通过操纵潜在的细胞可塑性来改善特定形式的认知功能障碍。

DESCRIPTION (provided by applicant): We are applying the economy-of-scale of the Drosophila model system to identify genes involved in plasticity. We have developed a Pavlovian olfactory learning assay that shows a wide variety of behavioral properties seen for associative learning across the animal kingdom. Most of the genes identified to date have been shown to be involved in various forms of behavioral or synaptic plasticity in both vertebrate and invertebrate model systems. We have identified a gene, Adf1, that plays a clear role in adult long-term memory formation (behavioral plasticity) and in synapse formation at the larval neuromuscular junction (developmental plasticity). The Adf1 gene encodes a transcription factor with no other known biological functions. We hypothesize that Adf1 is a molecular component of activity-dependent synaptic plasticity. We propose further experiments to (i) determine whether Adf1 interacts with other molecular components involved in synaptic plasticity, such as the cAMP (PKA) or jun kinase (JNK) signaling pathways, the CREB transcription pathway or cell adhesion molecules and (ii) visualize Adf1-dependent gene expression during developmental or behavioral. Ultimately, such knowledge will help to reveal various forms of cognitive dysfunction that result from heredity, disease, injury or age. Since the brain is a highly plastic organ, we eventually will be able to intervene with behavioral, pharmacological or even gene therapies to ameliorate specific forms of cognitive dysfunction by manipulating the underlying cellular plasticities.