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

描述(由申请者提供)：本项目的长期目标是了解学习如何影响嗅球内第一级处理的嗅觉气味表征。虽然哺乳动物的嗅觉系统已经被证明具有经历依赖经验的可塑性的非凡能力，但这种气味记忆是如何印记在成年嗅觉神经回路中的尚不清楚。虽然这个过程很可能涉及嗅觉通路的多个阶段的变化，但一个有趣的可塑性部位是嗅球小球层。在这一层内，感受器神经元输入的解剖结构允许气味信息转化为肾小球活动的气味特定地形图。这种活动模式可以在体内可视化使用新开发的转基因小鼠，其基于GFP的钙指示剂(G-Camp2)仅在突触后与受体输入的嗅球输出神经元中表达。与以前的成像方法不同，该鼠标首次允许我们观察肾小球层的纯突触后气味映射。使用这个小鼠模型，我们可以直接检验这样的假设，即嗅觉学习显着改变了突触后肾小球突触后气味对训练气味的表征。这将通过比较联合条件反射前后同一动物中气味诱发的肾小球活动模式来实现。初步数据表明，在训练后，使用给定气味的条件反射显著改变了肾小球对该气味的反应。在此基础上，我们计划通过测试以下假设来扩展我们的发现：这些变化将有助于减少训练过的气味和类似气味之间的表征重叠。总之，这些研究将对我们理解气味编码的神经基础以及可塑性在塑造神经对感觉刺激的反应中所起的作用产生重大影响。 与公共健康相关：嗅觉在我们的日常生活中扮演着重要的角色。嗅觉障碍通常是人类几种主要神经疾病的早期指标，包括阿尔茨海默病、帕金森氏病和精神分裂症。这项资助的总体目标是了解嗅觉处理的神经基础，这可能有助于这些疾病的诊断和治疗。

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.