Relating Synaptic Plasticity to Changes in Odor Representation and Perception

描述（申请人提供）：嗅觉系统提供了一个独特的强大的环境，在其中探索哺乳动物的感觉可塑性，因为嗅觉系统中最早的中央处理发生在嗅球的肾小球中，这是一种在动物模型中在体内物理和光学上可接近的结构，也因为分子遗传学技术的最新进展为这一领域的研究提供了极好的实验工具。使用分子遗传学工具和体内光学成像技术相结合，我最近表明，嗅觉系统表现出快速反馈突触前抑制从嗅觉神经释放的递质。我假设，这个电路的快速可塑性提供了自适应增益控制的主要感官输入从鼻子，从而发挥了重要作用，在编码的气味浓度和气味强度的感知。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检验这一假设，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的假设，即在感官环境的变化引起的可塑性在输入到嗅球的气味的代表。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气味质量和强度的感知。与公共卫生的相关性：哺乳动物的感觉系统不断变化，以适应其环境和经验。虽然我们已经很好地理解了某些感觉器官的适应性，但对于大脑中的回路如何改变以处理不同的感觉情况，我们知之甚少。需要对这个问题进行基础研究，以更好地为感觉问题患者的治疗提供信息，并促进人工传感器和其他潜在疗法的发展。

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.