The heat shock response in an identified neuronal circuit

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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.