In vivo optical imaging of experience-induced olfactory bulb glomerular plasticit

描述（由申请人提供）：该项目的长期目标是了解学习如何影响嗅球内第一层处理的嗅觉气味表征。虽然哺乳动物的嗅觉系统已被证明具有经历经验依赖的可塑性的非凡能力，但这种气味记忆如何在成人嗅觉神经回路中留下印记仍不清楚。虽然这个过程很可能涉及嗅觉通路多个阶段的变化，但一个有趣的可塑性部位是嗅觉肾小球层。在这一层中，受体神经元输入的解剖组织允许气味信息转化为肾小球活动的气味特异性地形图。这种活动模式可以用一种新开发的转基因小鼠在体内观察到，这种转基因小鼠具有一种基于gfp的钙指示剂（G-CaMP2），该指示剂仅在嗅球输出神经元突触后立即表达到受体输入。与以往的成像方法不同，这只小鼠允许我们首次在肾小球层观察纯粹的突触后气味图。利用这个小鼠模型，我们可以直接验证嗅觉学习显著改变嗅球突触后肾小球对训练过的气味者的气味表征的假设。这将通过比较气味诱发的肾小球活动模式在同一动物前后联想条件反射来完成。初步数据表明，在训练后，特定气味的调节显著改变了肾小球对该气味的反应。基于此，我们计划通过测试假设来扩展我们的发现，即这些变化将有助于减少训练过的气味者和类似气味者之间的代表性重叠。总之，这些研究将对我们理解气味编码的神经基础和可塑性在形成神经对感官刺激的反应中所起的作用产生重大影响。

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand how learning can influence olfactory odorant representations at the first level of processing within the olfactory bulb. While the mammalian olfactory system has been shown to have a remarkable capability for undergoing experience-dependent plasticity, how such odor memories are imprinted in the adult olfactory neural circuit remains unclear. Although this process most likely involves changes at multiple stages in the olfactory pathway, one interesting site for plasticity is the olfactory glomerular layer. Within this layer, the anatomical organization of receptor neuron input allows odorant information to be transformed into an odorant-specific topographical map of glomerular activity. This activity pattern can be visualized in vivo using a newly-developed transgenic mouse with a GFP-based calcium indicator (G-CaMP2) expressed exclusively in olfactory bulb output neurons immediately postsynaptic to receptor input. Unlike previous imaging methods, this mouse allows us to observed purely postsynaptic odor maps in the glomerular layer for the first time. Using this mouse model we can directly test the hypothesis that olfactory learning significantly alters olfactory bulb postsynaptic glomerular odorant representations for the trained odorant. This will be accomplished by comparing odorant-evoked glomerular activity patterns in the same animal before and after associative conditioning. Preliminary data suggests that conditioning with a given odorant significantly alters glomerular responses to that odorant following training. Based on this, we plan to extend our findings by testing the hypothesis that these changes will serve to reduce the representational overlap between the trained odorant and similar odorants. Together, these studies will have a significant impact on our understanding of the neural basis of odor coding and role plasticity plays in shaping neural responses to sensory stimuli. PUBLIC HEALTH RELEVANCE: The sense of smell plays an important role in our daily life. Olfaction dysfunction is often times an early indicator of several major neurological diseases in humans including Alzheimer's disease, Parkinson's disease, and schizophrenia. The general goal of this grant is to understand the neural basis of olfactory processing which could help in the diagnosis and treatment of these diseases.