COBRE: UVM BIOL PROJ 1: CHLORIDE HOMEOSTASIS IN OLFACTORY NEURONS AGING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。无法察觉气味是一个非常真实的障碍。嗅觉减退，这在老年人中很常见，可能导致营养不良。许多医学问题，如囊性纤维化和阿尔茨海默病，都可能导致嗅觉功能障碍。理解嗅觉系统的核心是确定输入，初级嗅觉感觉神经元（OSN）的功能;这是我们的长期目标。氯离子流量和细胞内氯离子水平在决定嗅觉神经元暴露于气味的最终结果方面是极其重要的：它是被刺激还是被抑制？氯离子水平起着至关重要的作用，但由于氯离子在信号转导途径中的作用较晚，因此与其他第二信使相比，对它的关注较少。我们正在测试的假设，Cl-稳态是必不可少的嗅觉神经元功能和改变[Cl]i改变气味反应。进度：MEQ荧光成像实验的结果表明，广泛的[Cl]i存在于孤立的OSN和[Cl]i水平保持恒定，除非细胞受到刺激。两个氯转运体，NKCC 1和KCC 2的抑制可以改变的气味反应，虽然似乎有第三个氯转运体的影响时，NKCC 1活性降低观察。免疫细胞化学染色显示NKCC 1和KCC 2位于纤毛和树突状突起上，这是气味传导的部位。这些Cl转运体如何调节仍不清楚，但[Cl]i在气味转导中起着不可或缺的作用，并可能决定气味反应是兴奋性还是抑制性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The inability to detect odors is a very real handicap. A diminished sense of smell, which is quite common in the elderly, can lead to malnutrition. A number of medical problems, such as cystic fibrosis and Alzheimer's disease, can cause olfactory dysfunction. Central to the understanding of the olfactory system is determining how the inputs, the primary olfactory sensory neurons (OSNs) function; this is our long-term goal. Chloride fluxes and intracellular chloride levels are extremely important in determining the ultimate outcome of the exposure of an olfactory neuron to odor: is it stimulated or inhibited? Chloride levels play an essential role, but because Cl- comes in late in the signal transduction pathway, less attention has been focused on it compared to other second messengers. We are testing the hypothesis that Cl- homeostasis is essential to olfactory neuron function and that changing [Cl]i alters odor responses. Progress: Results from MEQ fluorescence imaging experiments indicated that a wide range of [Cl]i exist in isolated OSNs and that [Cl]i levels remain constant unless the cell is stimulated. Inhibition of either of the two Cl transporters, NKCC1 and KCC2 can alter the odor response although there appears to be a 3rd Cl transporter whose effects were observed when NKCC1 activity was decreased. Immunocytochemistry on isolated OSNs showed the NKCC1 and KCC2 are located on the cilia and dentritic knob, the site of odor transduction. How these Cl transporters are regulated remains unclear but [Cl]i plays an integral role in odor transduction and probably determines if an odor response is excitatory or inhibitory.