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

经验诱导的嗅球肾小球可塑性的体内光学成像

• 批准号: 7573378
• 负责人: MAX L FLETCHER
• 金额: $ 15万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-02 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573378
• 关键词: Address; Adult; Affect; Aldehydes; Alzheimer' s Disease; Animals; Behavior; Behavioral; Biological Models; Calcium; Cells; Code; Data; Diagnosis; Disease; Dorsal; Food; Functional disorder; Goals; Grant; Human; Image; Individual; Learning; Life; Mammals; Maps; Memory; Mus; Neocortex; Neuraxis; Neurons; Odors; Olfactory Learning; Olfactory Pathways; Output; Parkinson Disease; Pathway interactions; Pattern; Perception; Play; Process; Reproduction; Rodent; Role; Schizophrenia; Sensory; Sensory Process; Series; Shapes; Site; Smell Perception; Source; Staging; Stimulus; Surface; Synapses; System; Testing; Time; Training; Transgenic Mice; aversive conditioning; base; calcium indicator; classical conditioning; conditioning; experience; imaging modality; imprint; in vivo; interest; mouse model; nervous system disorder; neural circuit; novel; olfactory bulb; optical imaging; postsynaptic; public health relevance; receptive field; receptor; relating to nervous system; response; sensor; sensory cortex; sensory stimulus; sensory system; social

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.

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级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非凡的经历依赖可塑性的能力，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。尽管这一过程很可能涉及嗅觉通路多个阶段的变化，但可塑性的一个有趣部位是嗅觉肾小球层。在这一层内，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拓扑图。这种活动模式可以使用新开发的转基因小鼠在体内可视化，该小鼠具有基于 GFP 的钙指示剂 (G-CaMP2)，该指示剂仅在紧邻受体输入的突触后嗅球输出神经元中表达。与以前的成像方法不同，这种小鼠首次使我们能够观察到肾小球层中纯粹的突触后气味图。使用该小鼠模型，我们可以直接测试嗅觉学习显着改变嗅球突触后肾小球气味表征的假设。这将通过比较同一动物在联想调节之前和之后由气味引起的肾小球活动模式来实现。初步数据表明，使用给定气味剂进行调节会显着改变训练后肾小球对该气味剂的反应。基于此，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经过训练的气味剂和类似气味剂之间的代表性重叠。总之，这些研究将对我们对气味编码的神经基础的理解以及可塑性在塑造对感觉刺激的神经反应中的作用产生重大影响。 公共卫生相关性：嗅觉在我们的日常生活中发挥着重要作用。嗅觉功能障碍通常是人类几种主要神经系统疾病的早期指标，包括阿尔茨海默病、帕金森病和精神分裂症。这笔赠款的总体目标是了解嗅觉处理的神经基础，这有助于诊断和治疗这些疾病。