Adf1 transcription in behaviorial & synaptic plasticity

Adf1 在行为中的转录

• 批准号: 7026468
• 负责人: TIM P TULLY
• 金额: $ 37.24万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7026468
• 关键词: Drosophilidae; JUN kinase; behavioral /social science research tag; biological signal transduction; cAMP response element binding protein; cell adhesion molecules; cyclic AMP; electrophysiology; gene expression; immunocytochemistry; in situ hybridization; laboratory rabbit; learning; memory; molecular genetics; molecular psychobiology; neural plasticity; neurogenetics; neuromuscular junction; neuropil; protein kinase A; synaptogenesis; transcription factor

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.

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识别与可塑性相关的基因。我们开发了一种巴甫洛夫嗅觉学习测定，它显示了整个动物界联想学习的各种行为特性。迄今为止发现的大多数基因已被证明与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有关。我们已经鉴定出一个基因 Adf1，它在成体长期记忆形成（行为可塑性）和幼虫神经肌肉接头突触形成（发育可塑性）中发挥着明显的作用。 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来（i）确定Adf1是否与参与突触可塑性的其他分子成分相互作用，例如cAMP（PKA）或jun激酶（JNK）信号通路、CREB转录通路或细胞粘附分子，以及（ii）可视化发育或行为过程中 Adf1 依赖性基因表达。最终，这些知识将有助于揭示由遗传、疾病、损伤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。