Adf1 transcription in behaviorial & synaptic plasticity

Adf1 在行为中的转录

• 批准号: 6704725
• 负责人: TIM P TULLY
• 金额: $ 38.04万
• 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/6704725
• 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来识别涉及可塑性的基因。我们已经开发了一种帕夫洛维亚的嗅觉学习测定法，该测定法显示了整个动物王国的关联学习的各种行为特性。迄今为止确定的大多数基因已被证明在脊椎动物和无脊椎动物模型系统中都以各种形式的行为或突触可塑性涉及。我们已经确定了一个基因ADF1，该基因在成人长期记忆形成（行为可塑性）和幼虫神经肌肉连接处的突触形成（发育塑性）中起着明显的作用。 ADF1基因编码没有其他已知生物学功能的转录因子。我们假设ADF1是活性依赖性突触可塑性的分子成分。我们提出了进一步的实验，以确定ADF1是否与突触可塑性涉及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转录途径或细胞粘附分子或在发育过程中可视化ADF1依赖性基因表达或行为。最终，这种知识将有助于揭示由于遗传，疾病，伤害或年龄而导致的各种形式的认知功能障碍。由于大脑是高度塑料器官，因此我们最终将能够干预行为，药理甚至基因疗法，从而通过操纵下面的细胞可塑性来改善特定形式的认知功能障碍。