Optical Imaging of Olfactory Sensory Code Transformation

嗅觉感官代码转换的光学成像

• 批准号: 8277392
• 负责人: Shin Nagayama
• 金额: $ 30.55万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277392
• 关键词: Afferent Neurons; Alzheimer' s Disease; Architecture; Behavior; Brain; Calcium; Cell physiology; Cells; Code; Data; Data Set; Dendritic Cells; Development; Diagnosis; Dimensions; Discrimination; Disease; Dyes; Eating; Electrophysiology (science); Flavoring; Functional Imaging; Functional disorder; Goals; Grant; Health; Image; Individual; Institutes; Label; Lateral; Life Style; Literature; Maps; Methods; Molecular Biology; Neurons; Nose; Obesity; Odors; Olfactory Nerve; Pathway interactions; Pattern; Penetration; Play; Population; Presynaptic Terminals; Process; Publishing; Quality of life; Research; Research Project Grants; Resolution; Role; Scheme; Science; Sensory; Sensory Process; Signal Transduction; Smell Perception; Staging; Structure; Surface; System; Testing; Tissues; Transgenic Mice; base; charge coupled device camera; combinatorial; human disease; in vivo; insight; interest; mouse model; neuronal cell body; novel; olfactory bulb; optical imaging; postsynaptic; presynaptic; relating to nervous system; response; sensor; spatiotemporal; two-photon

DESCRIPTION (provided by applicant): The long-term goal of this research is to understand how the olfactory system encodes odor information, and how olfactory sensory codes are transformed sequentially through different processing stages along the central projection pathways. Olfactory coding and processing have been extensively studied with two major approaches: (1) electrophysiology of single neurons, which can record neural activity at any tissue depth, but blindly without knowing network context in reference to upstream coding patterns; and (2) CCD camera imaging of spatiotemporal pattern of activated glomeruli, which is ideal for revealing the initial glomerulus-based codes, but lacks single-cell resolution and deep penetration required for exploring odor codes beyond the glomerular layer. This grant is aimed at bridging such a gap between single-cell physiology and large-scale CCD camera imaging, so as to unify the two large datasets already available in the literature. First, using a new transgenic mouse model, we will provide a direct comparison between the pre- and postsynaptic odor maps within the glomerular layer, and test the hypothesis that lateral circuits intrinsic to this layer can support interglomerular lateral inhibition and/or excitation for initial odor-map transformation. Second, by combining in vivo two-photon calcium imaging and targeted single-glomerulus dye labeling, we will perform a systematic analysis of odor ensemble codes carried by the mitral/tufted cells associated with a common glomerulus. We will test the hypothesis that both the overall size and distribution pattern of a glomerulus-defined active cell ensemble can be effective coding factors for odor intensity at least and maybe also identity. Finally, by imaging the mitral cell population with diverse glomerular projections, we will analyze the cross-glomerular odor ensemble responses in the context of corresponding glomerular activation patterns. We will study how the glomerulus-based odor codes break down into distributed mitral-cell population codes, and ask what is the benefit of redistributing odor signals which have just converged via the nose-to-bulb projection. Collectively, these studies should not only have a significant impact on our understanding of the neural basis of odor processing and discrimination, but could also yield novel and more general principles on how the brain transforms neural codes for achieving sensory and perceptive functions. PUBLIC HEALTH RELEVANCE The sense of smell plays an important role in our daily life style involving flavor and fragrance appreciation. Dysfunction of the olfactory system happens in many human diseases such as eating-related obesity and early development of Alzheimer's disease. The general goal of this grant in understanding the neural basis of odor coding and processing will not only help the diagnosis and treatment of these diseases, but will also promote people's life quality in general.

描述（由申请人提供）：本研究的长期目标是了解嗅觉系统如何编码气味信息，以及嗅觉感觉编码如何沿着中央投射路径通过不同的处理阶段依次转换。嗅觉编码和处理的研究主要有两种途径：(1)单个神经元的电生理学，它可以记录任何组织深度的神经活动，但盲目地不知道网络背景，参考上游编码模式；(2)激活肾小球的时空模式CCD相机成像，这是揭示初始肾小球基础密码的理想方法，但缺乏单细胞分辨率和深度穿透能力，无法探索肾小球层以外的气味密码。这项拨款旨在弥合单细胞生理学和大规模CCD相机成像之间的差距，从而统一文献中已有的两个大型数据集。首先，使用一种新的转基因小鼠模型，我们将提供肾小球层内突触前和突触后气味图谱之间的直接比较，并验证该层固有的侧回路可以支持肾小球间侧抑制和/或激发初始气味图谱转化的假设。其次，通过结合体内双光子钙成像和靶向单肾小球染色标记，我们将对与共同肾小球相关的二尖瓣/簇状细胞携带的气味集合编码进行系统分析。我们将验证一个假设，即肾小球定义的活性细胞群的总体大小和分布模式至少可以是气味强度的有效编码因素，也可能是识别的有效编码因素。最后，通过成像不同肾小球投影的二尖瓣细胞群，我们将分析相应肾小球激活模式下的跨肾小球气味集合反应。我们将研究基于肾小球的气味编码如何分解成分布的二尖瓣细胞群编码，并询问重新分配刚刚通过鼻子到球茎投影聚合的气味信号的好处。总的来说，这些研究不仅会对我们对气味处理和辨别的神经基础的理解产生重大影响，而且还可能产生关于大脑如何转换神经编码以实现感觉和感知功能的新颖和更一般的原理。嗅觉在我们的日常生活方式中扮演着重要的角色，包括对味道和香味的欣赏。嗅觉系统功能障碍发生在许多人类疾病中，如与饮食有关的肥胖和阿尔茨海默病的早期发展。这项资助的总体目标是了解气味编码和处理的神经基础，这不仅有助于这些疾病的诊断和治疗，而且还将提高人们的生活质量。

项目成果

Neuronal organization of olfactory bulb circuits.

• DOI: 10.3389/fncir.2014.00098
• 发表时间: 2014
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: Nagayama S;Homma R;Imamura F
• 通讯作者: Imamura F

Odorant response properties of individual neurons in an olfactory glomerular module.

• DOI: 10.1016/j.neuron.2013.01.022
• 发表时间: 2013-03-20
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Kikuta S;Fletcher ML;Homma R;Yamasoba T;Nagayama S
• 通讯作者: Nagayama S

Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex.

• DOI: 10.1523/jneurosci.0154-12.2012
• 发表时间: 2012-06-06
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Igarashi KM;Ieki N;An M;Yamaguchi Y;Nagayama S;Kobayakawa K;Kobayakawa R;Tanifuji M;Sakano H;Chen WR;Mori K
• 通讯作者: Mori K