Inhibitory mechanisms of odor intensity processing in the olfactory bulb

项目总结/摘要 抑制性中间神经元的亚群被假设为控制信息处理的机制， 大脑，如增益，调谐，正常化和灵敏度，但在整个神经系统中， 抑制性细胞类型仍然不清楚，并且大部分未被研究。在所有的感觉系统中，嗅球必须 进行刺激强度编码，因为没有处理气味强度的能力，动物无法 有效地觅食，交配，避免捕食，导致生存率下降，社会稀释 交互.这项工作扩展了以前的体外实验和测试预测从计算 神经回路模型首次在体内。新的双光子成像技术将被优化，以评估 抑制性（肾小球周围）和兴奋性（二尖瓣和簇状）细胞强度反应功能，同时在 在相同的麻醉或清醒动物和相同的肾小球中，在用相同的刺激期间， 一组除臭剂这种新方法将减少进行实验时出现的数据变化， 比较不同动物、神经回路和气味刺激的数据。该提案将使 在不同的细胞群体之间进行直接和新颖的比较。该提案还将建立独特的 两种抑制性中间神经元群（肾小球周围细胞和颗粒细胞）在形成兴奋性二尖瓣中的作用 和簇状细胞在清醒的气味强度依赖性处理过程中的反应。最近公布的方法， DREADD（设计者药物独家激活的设计者受体）的亚型特异性表达将 在这个提议中，我们将其应用于操纵清醒小鼠的肾小球周围和颗粒细胞抑制， 不同强度的样品气味剂。该建议将阐明基本的电路机制和作用 抑制性中间神经元用于嗅球中气味强度依赖性处理。

Project Summary/Abstract Subpopulations of inhibitory interneurons are hypothesized to control mechanisms of information processing in the brain, such as gain, tuning, normalization, and sensitivity, yet across neural systems, the unique roles of inhibitory cell types remain unclear and largely unstudied. As in all sensory systems, the olfactory bulb must conduct stimulus intensity coding, because without the ability to process odorant intensity, animals are unable to effectively forage, mate, and avoid predation, resulting in decreased survival rates and diluted social interactions. This work expands on previous in vitro experiments and tests predictions from computational neural circuit models for the first time in vivo. New two-photon imaging techniques will be optimized to assess inhibitory (periglomerular) and excitatory (mitral and tufted) cell intensity response functions simultaneously in vivo in the same anesthetized or awake animal and the same glomerulus during stimulation with the same panel of odorants. This new method will reduce data variability that arises when conducting experiments and comparing data across different animals, neural circuits, and odorant stimulations. This proposal will enable direct and novel comparisons across different cell populations. This proposal will also establish the unique roles of two inhibitory interneuron populations (periglomerular and granule cells) in shaping excitatory mitral and tufted cell responses during awake odor intensity dependent processing. Recently published methods for subtype specific expression of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) will be applied in this proposal to manipulate periglomerular and granule cell inhibition in awake mice while they sample odorants varying in intensity. This proposal will elucidate fundamental circuit mechanisms and the roles of inhibitory interneurons used in odor intensity dependent processing in the olfactory bulb.