SPATIAL AND TEMPORAL PROPERTIES OF GRANULE CELL RECRUITMENT IN THE MAMMALIAN OLFA

哺乳动物奥尔法颗粒细胞募集的空间和时间特性

• 批准号: 8594822
• 负责人: Shawn Denver Burton
• 金额: $ 4.22万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594822
• 关键词: Acute; Address; Afferent Neurons; Apical; Behavior; Calcium; Cell Communication; Cell Shape; Cells; Communication; Computer Simulation; Coupled; Cytoplasmic Granules; Data; Dendrites; Dependence; Discrimination; Electrophysiology (science); Image; Interneurons; Kinetics; Knowledge; Lateral; Link; Maps; Measures; Mediating; Monitor; Neurons; Odorant Receptors; Odors; Pattern; Performance; Population; Process; Property; Recruitment Activity; Recurrence; Research; Role; Sensory; Shapes; Slice; Smell Perception; Staging; Structure; Synapses; System; Testing; Time; Training; Tweens; Viral; Whole-Cell Recordings; Work; career; experience; extracellular; fundamental research; granule cell; in vivo; inhibitory neuron; insight; neural circuit; novel; olfactory bulb; optogenetics; preference; public health relevance; receptor; research study; response; skills; spatiotemporal; voltage clamp

DESCRIPTION (provided by applicant): The encoding of smell by the olfactory system is critical to mammalian communication and survival. Under- standing olfaction has proven extremely difficult, however, due to the vast diversity of odors, the large number of odor receptors, and the lack of any clear mapping of odor qualities. Fundamental research identifying the neural circuitry and basic computations performed in the olfactory system has thus been pivotal in elucidating principles of olfaction. In the olfactory bulb, sensory information is contained in precise spatiotemporal patterns of activity in mitral cells, the olfactory bulb princial neurons. These odor-specific patterns are generated in two stages. First, each mitral cell receives sensory input at a single input structure called a glomerulus. Odors activate specific but overlapping glomeruli, yielding poorly discriminable patterns of mitral cell input. Second, local inhibitory granule cells mediate lateral inhibition between mitral cells and decorrelate mitrl cell activity across time. Mitral cell-granule cell interactions thereby increase the discriminabilty of mitral cell activity patterns between different odors. Functional recruitment of granule cells i thus a critical step in olfaction, yet multiple fundamental questions remain concerning granule cell recruitment. First, what is the role of glomerular organization in granule cell recruitment? Anatomical data suggests that granule cells preferentially link mitral cells connected to the same glomerulus, but this spatial preference remains to be functionally confirmed. Second, how does the temporal sequence of mitral cell activity influence granule cell recruitment? The slow but input- specific kinetics of granule cell recruitment suggest that synchronous mitral cell activity may not be optimal for functionally recruiting granule cells. Thus, the primary objective of the proposed research is to investigate the spatial and temporal properties governing granule cell recruitment. Aim 1 of the proposed research is to test whether spatial glomerular organization controls granule cell recruitment. Feedforward input to granule cells will be compared across glomeruli using voltage-clamp recordings and extracellular and optogenetic glomerular stimulation, with the hypothesis that input will be strongest when stimulating a specific glomerulus. To test if granule cells preferentially link mitral cells connected to the same glomerulus, granule cell-mediated lateral inhibition will be compared between mitral cells connected to the same glomerulus and mitral cells connected to different glomeruli using paired voltage-clamp recordings. Aim 2 of the proposed research is to determine how the temporal sequence of mitral cell activity regulates granule cell recruitment. The temporal tuning of granule cell recruitment will first be measured using calcium imaging to monitor recruitment across large granule cell populations while stimulating neighboring glomeruli at varying temporal offsets. The influence of mitral cell syn- chrony on granule cell recruitment will then be directly examined using paired mitral cell recordings coupled with calcium imaging. Collectively, the proposed research will thus provide novel insight into a critical aspect of olfactory bulb circuitry: the sptial and temporal properties governing granule cell recruitment.

描述（由申请人提供）：嗅觉系统对气味的编码对于哺乳动物的交流和生存至关重要。然而，由于气味大量多样性，气味受体的多样性以及缺乏任何清晰的气味质量映射，因此被证明是极其困难的。因此，识别嗅觉系统中执行的神经回路和基本计算的基本研究在阐明嗅觉的原理中至关重要。在嗅球中，感官信息以二尖瓣细胞（嗅球鳞茎神经元）活性的精确时空模式包含。这些特定于气味的模式分为两个阶段。首先，每个二尖瓣细胞在称为肾小球的单个输入结构处接收感觉输入。气味激活特定但重叠的肾小球，产生二尖瓣输入的差异性模式。其次，局部抑制性颗粒细胞介导了二尖瓣细胞之间的侧面抑制作用，并介导了跨时间的MITRL细胞活性。二尖瓣细胞颗粒细胞相互作用，从而增加了不同气味之间二尖瓣细胞活性模式的区分。因此，颗粒细胞的功能募集是嗅觉中的关键一步，但有关颗粒细胞募集的多个基本问题仍然存在。首先，肾小球组织在颗粒细胞募集中的作用是什么？解剖学数据表明，颗粒细胞优先连接连接到同一肾小球的二尖瓣细胞，但是这种空间偏好仍有待确认。其次，二尖瓣活性的时间序列如何影响颗粒细胞募集？颗粒细胞募集的缓慢但输入的特异性动力学表明，同步二尖瓣活性可能不是功能募集颗粒细胞的最佳选择。因此，拟议的研究的主要目标是研究控制颗粒细胞募集的空间和时间特性。拟议研究的目标1是测试空间肾小球组织是否控制颗粒细胞募集。使用电压钳记录以及细胞外和光遗传学肾小球刺激，将比较颗粒细胞的进料输入，并假设输入在刺激特定的肾小球时的输入最强。为了测试颗粒细胞是否优先连接到相同肾小球连接的二尖瓣细胞，将使用成对的电压杆记录使用颗粒细胞介导的侧面抑制作用。拟议研究的目标2是确定二尖瓣活性的时间序列如何调节颗粒细胞募集。颗粒的时间调节 首先，将使用钙成像来测量细胞募集，以监测大型颗粒细胞群体的募集，同时刺激不同时间偏移时相邻的肾小球。然后，将使用配对的二尖瓣细胞记录与钙成像的配对二尖瓣记录直接检查二尖瓣细胞合成对颗粒细胞募集的影响。因此，拟议的研究将提供对嗅球电路的关键方面的新颖见解：管理颗粒细胞募集的Sptial和时间特性。