The heat shock response in an identified neuronal circuit

已识别神经元回路中的热休克反应

• 批准号: 10311042
• 负责人: Mara Rue
• 金额: $ 2.8万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311042
• 关键词: Address; Affect; Anoxia; Brain; Cells; Chemicals; Collection; Complex; Crab stomatogastric ganglion; Crustacea; Data; Exposure to; Family; Future; Ganglia; Gene Expression; Gene Expression Profiling; Genes; Global Change; Heat shock proteins; Heat-Shock Proteins 70; Heat-Shock Proteins 90; Heat-Shock Response; Heavy Metals; High temperature of physical object; Individual; Ion Channel; Knowledge; Lead; Measures; Messenger RNA; Metabolic; Metabolic stress; Modality; Molecular Chaperones; Motor; Motor Neurons; Nervous System Trauma; Nervous system structure; Neuroglia; Neurons; Output; Oxygen; Paper; Pattern; Physiological; Potassium; Preparation; Property; Protein Family; Proteins; Resistance; Saline; Shock; Specificity; Stress; Stroke; Synapses; System; Temperature; Trauma; Work; biophysical properties; central pattern generator; experience; extracellular; insight; interest; metal poisoning; neural circuit; neuronal circuitry; relating to nervous system; response; stressor; thermal stress

Project Summary The brain must constantly compensate for multiple destabilizing experiences while maintaining proper function. Adaptive responses to perturbation have been well documented in a wide number of systems. What is less well understood is how adaptation to one challenge affects the overall robustness of a circuit to other challenges. Of particular interest are heat shock proteins (HSP), a highly conserved family of molecular chaperones that are upregulated in the nervous system in response to a wide range of stressors. The proposed work addresses the specificity of the heat shock response to different perturbations using a well described small motor circuit, the crab stomatogastric ganglion (STG). Previous work in the STG has established the robustness of its motor neurons to high temperatures, altered pH and elevated extracellular potassium. This wealth of knowledge allows me to compare the effect of three sub- critical perturbations across the same set of identified neurons. Preliminary data on pooled neurons indicates that different subsets of HSPs are activated in the STG in response to high temperatures compared to elevated potassium concentrations. I will now compare the activation of HSP and other gene expression changes across three perturbations in individual identified neurons. The proposed work will address how the neuronal response to one perturbation may be generally neuroprotective, and how the response may be specific to individual challenges. The direct effects of HSP on the intrinsic properties of STG neurons will be determined. The F-I curves, threshold and resistance of neurons will be determined both before and after application of HSP70 to determine what specific effects HSP70 can have on intrinsic properties of identified neurons. In addition, I will measure how such changes in intrinsic properties confer robustness to future perturbation.

项目摘要 大脑必须不断地补偿多个不稳定的经历，同时保持适当的 功能。对扰动的适应性反应已经在许多系统中得到了很好的证明。是什么 较少了解的是，适应一个挑战如何影响电路对另一个挑战的整体健壮性 挑战。特别令人感兴趣的是热休克蛋白(HSP)，这是一个高度保守的分子家族 神经系统中对各种应激源做出反应而上调的伴侣蛋白。建议数 这项工作解决了热休克反应对不同扰动的特异性，使用了一个描述得很好的小的 运动回路，蟹的口胃神经节(STG)。 先前在STG上的研究已经建立了其运动神经元对高温、pH变化的健壮性 以及升高的细胞外钾。这一丰富的知识使我能够比较三个分项的效果 在同一组已识别的神经元上的临界扰动。关于汇聚神经元的初步数据表明 与高温相比，热休克蛋白的不同子集在STG中被激活以响应高温 钾浓度。我现在将比较热休克蛋白的激活和其他基因表达的变化 在单个识别的神经元中有三个扰动。这项拟议的工作将解决神经元如何 对一种干扰的反应通常可能是神经保护的，以及这种反应可能是如何特异性的 个人挑战。 热休克蛋白对STG神经元内在特性的直接影响将被确定。F-I曲线， 在应用HSP70前后将测定神经元的阈值和阻力 确定HSP70对已识别神经元的固有属性有什么特定影响。另外，我会 衡量这种内在属性的变化如何增强对未来扰动的稳健性。