Using functionally-defined glomeruli to probe circuit function in the mammalian olfactory bulb

使用功能定义的肾小球探测哺乳动物嗅球的电路功能

• 批准号: 9791032
• 负责人: DALE M WACHOWIAK
• 金额: $ 38.19万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791032
• 关键词: Adaptive Behaviors; Afferent Neurons; Animals; Behavior; Behavioral Assay; Biological Models; Brain; Cells; Code; Communities; Complex; Data; Detection; Diagnostic; Dorsal; Goals; Image; Individual; Interneurons; Knowledge; Lateral; Lead; Maps; Mediating; Modality; Modeling; Nature; Nervous system structure; Neurons; Neurosciences; Odorant Receptors; Odors; Olfactory Pathways; Organ; Output; Play; Population; Positioning Attribute; Problem Solving; Process; Property; Prosthesis; Resources; Role; Sensory; Sensory Process; Shapes; Smell Perception; Specificity; Stimulus; System; Testing; Therapeutic; Time; behavioral response; cell type; driving behavior; experience; experimental study; glomerular function; improved; in vivo; information processing; innovation; insight; network models; neural circuit; novel; olfactory bulb; olfactory bulb glomeruli; olfactory sensory neurons; olfactory stimulus; operation; predictive modeling; relating to nervous system; response; sensory input; sensory system; transmission process

PROJECT SUMMARY We seek to better understand how the brain processes olfactory information by focusing on how circuits of the olfactory bulb control two fundamental aspects of sensory processing: the relationship between sensory input and olfactory bulb output as a function of stimulus intensity, and tuning of response specificity by lateral inhibition. Models of how olfactory bulb circuits mediate these operations exist, but generating and testing rigorous predictions from them has been limited by a lack of understanding of how circuits are organized with respect to olfactory bulb glomeruli. Glomeruli represent individual odorant receptors and so constitute the fundamental unit of information processing at this stage. Our strategy is to overcome this gap by, first, better defining the functional map of odor 'space' across glomeruli of the dorsal olfactory bulb. To achieve this we will functionally define glomeruli in terms of the odorants to which they have maximal sensitivity as well as their relative sensitivities across a carefully-selected odorant panel, yielding the first `odor sensitivity' map of the dorsal olfactory bulb and allowing for the rapid and reliable identification of individual glomeruli across animals. We will use these data to uncover new insights into the organization of glomerular odor maps and to generate a public resource for further exploration by the neuroscience community. We will next use this knowledge to rigorously test alternative models for how specific circuits shape the input-output functions of the olfactory bulb by comparing intensity-response functions of sensory inputs and glomerular outputs and by selectively removing particular interneuron types from the olfactory bulb network. We will also test alternative models for how inhibitory connections between different glomeruli are organized and how they may be shaped by odor experience, using odorants that selectively activate different combinations of identified glomeruli. Our experimental strategy builds on innovative approaches that are key to achieving a new level of understanding of how odor representations are transformed by olfactory bulb circuits. First, we are able to repeatedly identify and target many glomeruli across the dorsal olfactory bulb using a small number of diagnostic odorants and to efficiently map responses to many odorants in a single experiment. Second, we are able to selectively image from sensory inputs to glomeruli, projection neuron outputs from glomeruli, or both simultaneously, allowing us to precisely characterize input-output transformations by olfactory circuits. Finally, we will develop an improved model of the olfactory bulb network that is highly constrained by experimental data and which should lead to new insights into how this network alters odor representations and enable new predictions that can be tested with further circuit manipulations or behavioral assays.

项目摘要 我们试图通过关注回路如何更好地理解大脑如何处理嗅觉信息， 嗅球控制感觉处理的两个基本方面：感觉之间的关系， 输入和嗅球输出作为刺激强度的函数，并通过横向调节反应特异性 抑制作用模型如何嗅球电路调解这些操作存在，但产生和测试 由于缺乏对电路如何组织的理解，他们的严格预测受到限制， 关于嗅球小球。肾小球代表个体气味受体，因此构成了 信息处理的基本单位。 我们的策略是克服这一差距，首先，更好地定义气味“空间”的功能图， 背侧嗅球的肾小球。为了实现这一点，我们将从功能上定义肾小球， 它们具有最大敏感性的气味剂以及它们在仔细选择的环境中的相对敏感性。 气味面板，产生背嗅球的第一个“气味敏感性”图，并允许快速和 可靠地鉴定动物中的单个肾小球。我们将利用这些数据来揭示新的见解， 肾小球气味地图的组织，并产生一个公共资源，供进一步探索 神经科学社区接下来，我们将使用这些知识来严格测试替代模型， 电路通过比较以下信号的强度-响应函数来塑造嗅球的输入-输出函数： 感觉输入和肾小球输出，并通过选择性地去除特定的中间神经元类型， 嗅球网络我们还将测试替代模型如何抑制不同之间的连接 肾小球的组织，以及它们如何通过气味经验来塑造，使用选择性地 激活不同的肾小球组合。 我们的实验策略建立在创新方法的基础上，这些方法是实现新水平的关键。 了解气味表征是如何被嗅球回路转化的。首先，我们能够 重复识别和靶向许多肾小球在背嗅球使用少量的 诊断气味剂，并在单一实验中有效地映射对许多气味剂的反应。第二，我们 能够选择性地从到肾小球感觉输入、来自肾小球的投射神经元输出或两者成像 同时，使我们能够精确地表征嗅觉回路的输入-输出转换。 最后，我们将开发一个改进的嗅球网络模型，该模型高度受限于 实验数据，这应该导致新的见解，如何这个网络改变气味表征， 实现新的预测，可以用进一步的电路操作或行为分析来测试。