Cellular Mechanisms of Learning and Memory in Drosophila

果蝇学习和记忆的细胞机制

• 批准号: 8301520
• 负责人: SUBHABRATA SANYAL
• 金额: $ 19.38万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301520
• 关键词: Adaptive Behaviors; Address; Adult; Animal Model; Architecture; Area; Behavior; Behavioral; Biological; Biological Assay; Brain; Brain region; Cells; Cholinergic Receptors; Communities; Computational algorithm; Coupled; Dendrites; Development; Drosophila genus; Family; Future; GABA Receptor; Gene Expression; Genetic; Genetic Techniques; Genetic Transcription; Glutamates; Growth; Image; Imaging Techniques; In Vitro; Individual; Interneurons; Label; Laboratories; Lateral; Learning; Measurement; Measures; Membrane; Memory; Memory impairment; Methods; Microscopic; Molecular; Motor Neurons; Nervous system structure; Neuraxis; Neuronal Plasticity; Neurons; Neurosciences; Odors; Outcome; Phenotype; Preparation; Property; Reagent; Regulation; Reporting; Resolution; Role; Sensory; Serine; Signal Pathway; Signal Transduction; Synapses; Synaptic Receptors; Synaptic plasticity; System; Tadpoles; Techniques; Technology; Tectum Mesencephali; Testing; Transcriptional Regulation; Transgenic Organisms; Translations; Use of New Techniques; Vertebral column; base; calmodulin-dependent protein kinase II; design; fly; functional outcomes; genetic analysis; in vivo; in vivo Model; insight; long term memory; mutant; neglect; neurogenetics; novel; patch clamp; platform-independent; programs; protein expression; reconstruction; relating to nervous system; research study; tool; transcription factor

DESCRIPTION (provided by applicant): This proposal describes the development and optimization of novel reagents and technologies to measure and experimentally perturb growth and activity-dependent plasticity of neuronal dendrites in Drosophila central nervous system neurons in vivo and examine their outcome on long-term behavioral adaptation. These techniques effectively combine behavioral analysis on one hand with transgenic labeling of individual central nervous system neurons with visible fluorescent markers (e.g. GFP), concomitant expression of proteins of choice in these neurons, confocal microscopic imaging of neuronal dendrites, and 3D reconstruction of these dendrites using dedicated computer algorithms on the other. We use this suite of techniques to test the hypothesis that the Myb-related transcription factor Adf-1 regulates learning and memory in Drosophila by controlling structural and functional properties of neuronal dendrites, downstream of a signaling pathway driven by CaMKII, as proof of principle. Adf-1 is expressed widely in the fly nervous system including motor neurons and higher brain regions required for learning and memory, similar to reported Myb expression in the vertebrate brain. Strikingly, mutants in Adf-1 (called nalyot) are also reported to have dramatic deficits in long-term memory formation. Results obtained thus far suggest Adf-1 strongly regulates dendrite growth. Based on these observations, we propose that neuronal Adf-1, by regulating activity- dependent plasticity of neuronal dendrites, instructs cellular mechanisms that control long-term behavioral adaptation (including learning and memory). Upon conclusion, these studies should not only reveal fundamental molecular mechanisms that, through regulation of activity-dependent dendritic plasticity, control learning and memory, but also firmly establish widely useful techniques to measure structural and functional plasticity of dendrites in the context of long-term behavioral adaptation.

描述（由申请人提供）：本提案描述了新型试剂和技术的开发和优化，以测量和实验性干扰果蝇中枢神经系统神经元中神经元树突的生长和活性依赖性可塑性，并检查其对长期行为适应的结果。这些技术一方面有效地将联合收割机行为分析与用可见荧光标记物（例如GFP）对个体中枢神经系统神经元的转基因标记、在这些神经元中选择的蛋白质的伴随表达、神经元树突的共聚焦显微成像以及另一方面使用专用计算机算法对这些树突的3D重建相结合。我们使用这套技术来测试的假设，Myb相关的转录因子Adf-1调节果蝇的学习和记忆通过控制神经元树突的结构和功能特性，下游的信号通路驱动的CaMKII，作为原则的证据。Adf-1在果蝇神经系统中广泛表达，包括运动神经元和学习和记忆所需的高级脑区域，类似于报道的Myb在脊椎动物脑中的表达。引人注目的是，Adf-1（称为nalyot）的突变体也被报道在长期记忆形成方面存在严重缺陷。迄今为止获得的结果表明Adf-1强烈调节枝晶生长。基于这些观察，我们提出神经元Adf-1通过调节神经元树突的活性依赖性可塑性，指导控制长期行为适应（包括学习和记忆）的细胞机制。总之，这些研究不仅应该揭示基本的分子机制，通过活动依赖性树突可塑性的调节，控制学习和记忆，但也牢固地建立广泛有用的技术来测量树突的结构和功能的可塑性的背景下，长期的行为适应。

项目成果

Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulates Drosophila motoneuron dendrite development

受体表达、神经活动和 AP-1 依赖性转录之间的时间一致性调节果蝇运动神经元树突发育

• DOI: 10.1242/dev.089235
• 发表时间: 2013
• 期刊: Development
• 影响因子: 4.6
• 作者: Vonhoff F;Kühn C;Blumenstock S;Sanyal S;Duch C.
• 通讯作者: Duch C.

Sleep fragmentation and motor restlessness in a Drosophila model of Restless Legs Syndrome.

• DOI: 10.1016/j.cub.2012.04.027
• 发表时间: 2012-06-19
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Freeman, Amanda;Pranski, Elaine;Miller, R. Daniel;Radmard, Sara;Bernhard, Doug;Jinnah, H. A.;Betarbet, Ranjita;Rye, David B.;Sanyal, Subhabrata
• 通讯作者: Sanyal, Subhabrata