Circuit architecture and dynamics representation in odor perception

气味感知中的电路架构和动态表示

• 批准号: 9096828
• 负责人: Thomas A Cleland
• 金额: $ 58.99万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096828
• 关键词: Address; Affect; Animals; Applied Genetics; Architecture; Area; Axon; Behavior; Behavioral; Behavioral Assay; Behavioral Genetics; Biological Assay; Brain; Cells; Code; Cognitive deficits; Dendrites; Detection; Development; Discrimination; Electrodes; Electrophysiology (science); Employee Strikes; Environment; Feedback; Genetic; Goals; Habitats; Image; Individual; Intervention; Lateral; Learning; Life; Maps; Mental disorders; Methodology; Modeling; Mus; Mutant Strains Mice; Nervous system structure; Neurons; Odorant Receptors; Odors; Olfactory Learning; Olfactory Pathways; Pattern; Perception; Play; Population; Process; Resolution; Role; Sensory; Signal Transduction; Specificity; Stereotyping; Stimulus; Structure; Testing; Theoretical model; Training; base; driving behavior; experience; genetic manipulation; improved; information processing; insight; mathematical model; mitral cell; olfactory bulb; olfactory bulb glomeruli; olfactory sensory neurons; optical imaging; piriform cortex; predicting response; public health relevance; receptor; relating to nervous system; research study; response; segregation; sensor; sensory system; tool

 DESCRIPTION (provided by applicant): In the mammalian brain, early sensory areas are organized as stereotyped maps of stimulus qualities. The anatomical features of these sensory maps underlie the neuronal computations and information processing that are essential to generate appropriate perceptual experiences and behaviors. In the mammalian olfactory bulb (OB), the most striking anatomical feature of this sensory map is the convergent axonal input from primary olfactory sensory neurons (OSNs); specifically, each insular glomerular structure in the OB receives axons exclusively from OSNs expressing the same odorant receptor. Moreover, OB projection neurons, the mitral/tufted cells, also project their primary dendrites exclusively into a single glomerulus. However, it is not well understood how this strict pattern of convergence and segregation contributes materially to the processing of olfactory information and odor-driven behaviors. In this project, we establish a multi-disciplinary approach to determine the contribution of this strict anatomical mapping to odor representation and perception. Specifically, we will genetically manipulate the projection patterns of OSN populations to perturb the anatomical map in the olfactory bulb, and perform a battery of automated behavioral assays probing odor discrimination and recognition. We then will integrate mathematical models based on OB circuitry with electrophysiological and optical imaging studies to elucidate the basis for these response differences in wildtype and mutant mice. By combining genetics, behavior, electrophysiological, and imaging approaches, we will determine the impact of genetically altered glomerular maps on odor perception under both naïve and learned conditions. RELEVANCE: Precise neuronal connectivity in the nervous system is essential for its proper function. Cognitive deficits in many psychiatric disorders arise from disruptions in neural connectivity, including disruptions within sensory circuits. The proposed study investigates the role of a specialized, anatomical neuronal connectivity pattern in regulating sensory information processing and perceptual experience. Results from this study will reveal how brain function can deteriorate because of disruptions in the normal connection patterns among neurons.

 描述（由申请人提供）：在哺乳动物大脑中，早期感觉区域被组织为刺激质量的刻板地图。这些感觉地图的解剖学特征是神经元计算和信息处理的基础，这些计算和信息处理对于产生适当的感知体验和行为至关重要。在哺乳动物的嗅球（OB），这个感觉地图的最显着的解剖特征是会聚轴突输入初级嗅觉感觉神经元（OSN），具体地说，在OB中的每个岛状肾小球结构接收轴突专门从OSN表达相同的气味受体。此外，OB投射神经元，二尖瓣/簇状细胞，也将其初级树突专门投射到单个肾小球中。然而，人们并不清楚这种严格的模式是如何形成的。 会聚和分离对嗅觉信息的处理和气味驱动的行为有重要贡献。在这个项目中，我们建立了一个多学科的方法来确定这种严格的解剖映射的气味表示和感知的贡献。具体来说，我们将从遗传学上操纵OSN群体的投射模式，以扰乱嗅球中的解剖图，并进行一系列自动行为测定，以探测气味辨别和识别。然后，我们将整合OB电路与电生理学和光学成像研究的基础上的数学模型，以阐明野生型和突变小鼠的这些反应差异的基础。通过结合遗传学、行为学、电生理学和成像方法，我们将确定遗传改变的肾小球地图在幼稚和学习条件下对气味感知的影响。 相关性：神经系统中精确的神经元连接对其正常功能至关重要。许多精神疾病的认知缺陷源于神经连接的中断，包括感觉回路的中断。拟议的研究调查的作用，一个专门的，解剖神经元连接模式在调节感觉信息处理和知觉经验。这项研究的结果将揭示大脑功能如何因为神经元之间正常连接模式的中断而恶化。