Relating Synaptic Plasticity to Changes in Odor Representation and Perception

描述(申请人提供)：嗅觉系统为探索哺乳动物的感觉可塑性提供了一个独特的强大环境，因为嗅觉系统中最早的中央处理发生在嗅球的肾小球中，这种结构在动物模型中是物理和光学的，而且最近分子基因技术的进步为这一领域的研究提供了极好的实验工具。结合分子遗传学工具和活体光学成像技术，我最近发现，嗅觉系统表现出对嗅神经递质释放的快速反馈突触前抑制。我推测，这个回路的快速可塑性为来自鼻子的初级感觉输入提供了自适应的增益控制，因此在气味浓度的编码和气味强度的感知中发挥了主要作用。此外，初步数据表明，这种抑制回路可能会随着时间的推移而改变，以适应嗅觉环境的变化。这些实验的第一个目的是验证这样一个假设，即初级感觉输入到嗅球的突触前调制有助于气味浓度的编码。这些实验的第二个目的是使用光学成像技术来测试这一假设，即感觉环境的变化导致嗅球输入端气味表征的可塑性。这些实验的最终目的是使用行为分析来测试这种可塑性如何影响对气味质量和强度的感知。与公共卫生相关：哺乳动物的感觉系统不断变化，以适应它们的环境和经验。虽然人们对某些感官的适应已有很好的了解，但对大脑中的回路如何改变以处理不同的感觉情况却知之甚少。需要对这个问题进行基础研究，以便更好地为有感觉问题的患者的治疗提供信息，并加强人工传感器和其他潜在疗法的开发。

DESCRIPTION (provided by applicant): The olfactory system provides a uniquely powerful environment in which to explore sensory plasticity in mammals, because the earliest central processing in the olfactory system takes place in the glomeruli of the olfactory bulb, a structure that is physically and optically accessible in vivo in animal models, and because recent advances in molecular genetic technology have produced excellent experimental tools for studies in this area. Using a combination of molecular genetic tools and in vivo optical imaging techniques, I have recently shown that the olfactory system exhibits rapid feedback presynaptic inhibition of transmitter release from the olfactory nerve. I hypothesize that the rapid plasticity of this circuit provides adaptive gain control for the primary sensory input from the nose, and thus plays a major role in the encoding of odorant concentration and the perception of odor intensity. Moreover, preliminary data suggest that this inhibitory circuitry may change over time to accommodate changes in the olfactory environment. The first aim of these experiments is to test the hypothesis that this presynaptic modulation of primary sensory input to the olfactory bulb contributes to the encoding of odor concentration. The second aim of these experiments is to use optical imaging techniques to test the hypothesis that changes in sensory environment induces plasticity in the representation of odors at the input to the olfactory bulb. The final aim of these experiments is to use behavioral assays to test how this plasticity affects the perception of odor quality and intensity. Relevance to Public Health: Mammalian sensory systems constantly change to adapt to their environment and experience. While adaptation in some sensory organs is well understood, much less is known about how circuitry in the brain changes to handle different sensory situations. Basic research into this question is needed to better inform the treatment of patients with sensory problems and to enhance the development of artificial sensors and other potential therapies.