Adf1 transcription in behaviorial & synaptic plasticity

描述（由申请人提供）：我们正在应用果蝇模型系统的规模经济来鉴定涉及可塑性的基因。我们已经开发了一个巴甫洛夫嗅觉学习试验，显示了各种各样的行为特性，在整个动物王国的联想学习。迄今为止，已发现的大多数基因在脊椎动物和无脊椎动物模型系统中参与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，在成人长期记忆的形成（行为可塑性）和突触的形成在幼虫神经肌肉接头（发育可塑性）中起着明确的作用。Adf1基因编码的转录因子没有其他已知的生物学功能。我们假设Adf1是活动依赖性突触可塑性的分子组成部分。我们提出进一步的实验，以（i）确定是否Adf1与其他分子组件参与突触可塑性，如cAMP（PKA）或jun激酶（JNK）信号通路，CREB转录通路或细胞粘附分子和（ii）可视化Adf1依赖的基因表达在发育或行为。最终，这些知识将有助于揭示由遗传、疾病、伤害或年龄引起的各种形式的认知功能障碍。由于大脑是一个高度可塑性的器官，我们最终将能够通过行为、药理学甚至基因疗法进行干预，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.