Functional Organization of the Olfactory Cortex

嗅觉皮层的功能组织

• 批准号: 7190277
• 负责人: Zhihua Zou
• 金额: $ 18.88万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-05 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7190277
• 关键词: Afferent Neurons; Aging; Animals; Applied Genetics; Area; Axon; Biological; Brain; Cells; Chemicals; Chromosome Pairing; Complex; Condition; Defect; Detection; Development; Disease; Early Diagnosis; Exploratory/Developmental Grant; Fire - disasters; Gene Targeting; Genetic; Green Fluorescent Proteins; Imagery; Individual; Injection of therapeutic agent; Knowledge; Label; Lead; Maps; Mediating; Methods; Molecular; Molecular Genetics; Mus; Neurodegenerative Disorders; Neurons; Nose; Odorant Receptors; Odors; Olfactory Cortex; Olfactory Epithelium; Pathway interactions; Pattern; Perception; Property; Psyche structure; Pyramidal Cells; Recombinant adeno-associated virus (rAAV); Research Personnel; Research Project Grants; Sensory; Shapes; Signal Transduction; Smell Perception; Specificity; Stereotyping; Structure; Surveys; Synapses; System; Techniques; Testing; Time; Tracer; Transgenic Mice; Translating; Travel; Vomeronasal Systems; base; embryonic stem cell; neural circuit; novel; olfactory bulb; programs; receptor; relating to nervous system; response; sensory stimulus; sensory system; stem; tool

DESCRIPTION (provided by applicant): Loss of smell is one of the first signs of many neurodegenerative diseases and aging disorders. Knowledge of neuronal structure and the pathways of information flow in the brain is important for identifying the cause of smell loss in diseased brains which may lead to early diagnosis and better treatment of the underlying conditions. Studies in the past have uncovered much about the mechanisms of odor detection in the mouse olfactory epithelium and bulb, but little is known about how sensory information is encoded in the cortex. We previously showed that inputs derived from different types of odorant receptors (ORs) are targeted to different but spatially overlapping clusters of cortical neurons and each cortical neuron appears to receive inputs from multiple ORs. Given that each odor molecule is detected in the nose by a combination of different ORs, this proposal will develop and apply genetic and functional approaches to test if inputs from the different ORs activated by the same odorant converge on cortical neurons to determine their response specificity. In Aim 1, we will develop recombinant adeno-associated virus (rAAV) to express different transneuronal tracers. As each bulb glomerulus represents a single type of OR, we will inject different rAAVs into different glomeruli to express a distinct tracer in bulb mitral and tufted cells connected to the injected glomeruli. The tracer will migrate from bulb to cortex to reveal the cortical organization of the corresponding ORs. These studies will test if inputs from the ORs activated by the same odorant converge on cortical neurons. In Aim 2, we will examine if the neurons activated by an odorant are those that receive convergent inputs from its ORs. In addition, we will compare the cortical neurons activated by separate versus combined OR inputs to test if combinations of OR inputs shape the response specificity of cortical neurons. Together, these studies will show how different chemical features detected by different ORs are integrated in the cortex to yield distinct perceptions. The new tracing method developed in this proposal will also be useful to systematically analyze how the stereotyped bulb map is topographically represented in the cortex and if different odor qualities are represented by distinct cortical patterns. The proposed studies are ideally suited for the R21 mechanism.

描述（由申请人提供）：嗅觉丧失是许多神经退行性疾病和衰老疾病的最初迹象之一。了解大脑中的神经元结构和信息流途径对于确定患病大脑中嗅觉丧失的原因非常重要，这可能导致早期诊断和更好地治疗潜在疾病。过去的研究已经揭示了小鼠嗅上皮和嗅球中气味检测的机制，但对感觉信息如何在皮层中编码知之甚少。我们以前表明，来自不同类型的气味受体（OR）的输入针对不同的，但空间上重叠的皮质神经元簇，每个皮质神经元似乎从多个OR接收输入。鉴于每个气味分子在鼻子中被不同的OR的组合检测到，该提案将开发和应用遗传和功能方法来测试来自相同气味剂激活的不同OR的输入是否会聚集在皮层神经元上，以确定它们的反应特异性。目的一：利用重组腺相关病毒（rAAV）表达不同的跨神经元示踪剂。由于每个球肾小球代表单一类型的OR，我们将不同的rAAV注射到不同的肾小球中，以在与注射的肾小球连接的球二尖瓣和簇状细胞中表达不同的示踪剂。示踪剂将从球迁移到皮质，以显示相应OR的皮质组织。这些研究将测试来自被相同气味剂激活的OR的输入是否会聚集在皮层神经元上。在目标2中，我们将检查被气味剂激活的神经元是否是那些从其OR接收收敛输入的神经元。此外，我们将比较单独与组合OR输入激活的皮层神经元，以测试OR输入的组合是否会塑造皮层神经元的反应特异性。总之，这些研究将展示不同OR检测到的不同化学特征如何整合到皮层中，以产生不同的感知。在这个建议中开发的新的跟踪方法也将是有用的，系统地分析如何定型灯泡地图的地形表示在皮层，如果不同的气味质量是由不同的皮层模式。所提出的研究非常适合R21机制。