The heat shock response in an identified neuronal circuit

项目摘要 大脑必须不断地补偿多种不稳定的经验，同时保持适当的 功能对扰动的适应性反应在许多系统中都有很好的记载。是什么 不太清楚的是，对一种挑战的适应如何影响电路对其他挑战的整体鲁棒性。 挑战特别感兴趣的是热休克蛋白（HSP），一个高度保守的分子家族， 在神经系统中响应于广泛的应激源而上调的伴侣蛋白。拟议 工作解决了特异性的热休克反应不同的扰动使用一个良好的描述小 运动回路，蟹口胃神经节（STG）。 以前在STG中的工作已经建立了其运动神经元对高温，改变pH值的鲁棒性 和细胞外钾升高这些丰富的知识使我能够比较三个子的效果， 在同一组已识别的神经元上的临界扰动。对混合神经元的初步数据表明 不同的HSP亚群在STG中响应于高温而被激活， 钾浓度我现在将比较HSP的激活和其他基因表达的变化， 三个扰动在个别识别的神经元。这项工作将解决神经元如何 对一种扰动的反应通常可以是神经保护性的，并且该反应如何可以特异于 个人挑战。 将确定HSP对STG神经元内在特性的直接影响。F-I曲线， 将在应用HSP 70之前和之后测定神经元的阈值和电阻， 确定HSP 70对已识别神经元的内在特性有哪些具体影响。此外，我将 测量这种内在属性的变化如何赋予未来扰动的鲁棒性。

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.