Modulation of Glomerular Function

描述（由申请人提供）：嗅觉系统的感觉输入最初由嗅球（OB）肾小球中的神经回路处理。这个回路的目标是来自神经调节中心的离心输入。通过二尖瓣/簇状（MT）细胞的OB输出显示了清醒动物的感觉反应的显着调制。了解这些气味信息处理的最早阶段是如何调制的，对于充分理解嗅觉系统功能至关重要。本项目将首次研究乙酰胆碱（ACh）和5-羟色胺（5 HT）如何调节肾小球回路中的感觉处理。这项研究建立在我们对这些电路的理解及其在OB输出整形中的重要性的最新进展之上。该项目将整合OB切片和麻醉和清醒的头部固定小鼠的信息。这种多维的方法旨在将肾小球回路的调制与特定神经调节系统的激活联系起来-来自斜角带的胆碱能输入和来自中缝核的胆碱能输入。我们的工作假设是，ACh和5-HT差异调节肾小球加工，以形成突触前和突触后抑制以及MT细胞的兴奋性。我们进一步假设，ACh调制减少感觉输入的影响，同时增加MT细胞的兴奋性。这可以限制气味检测，但增加辨别能力。这项拟议的研究是两名研究人员的高度综合努力，旨在了解麻醉和未麻醉动物中从细胞和回路到单个神经元的早期嗅觉处理的调制。

DESCRIPTION (provided by applicant): Sensory inputs to the olfactory system are initially processed by neural circuits in olfactory bulb (OB) glomeruli. This circuitry is targeted by centrifugal inputs from neuromodulatory centers. OB output via mitral/tufted (MT) cells shows remarkable modulation of sensory responses in the awake animal. Knowing how these earliest stages of odor information processing are modulated is critical to fully understanding olfactory system function. This project will investigate - for the first time - how acetylcholine (ACh) and serotonin (5HT) modulate sensory processing in glomerular circuits. The research builds on recent advances in our understanding of these circuits and their importance in shaping OB output. The project will integrate information from OB slices and anesthetized and awake head-fixed mice. This multidimensional approach aims to link the modulation of glomerular circuits to the activation of specific neuromodulatory systems - cholinergic inputs from the diagonal band and serotonergic inputs from the raphe nuclei. Our working hypothesis is that ACh and 5HT differentially modulate glomerular processing to shape both pre- and postsynaptic inhibition as well as MT cell excitability. We further hypothesize that ACh modulation reduces the impact of sensory input while at the same time increasing the excitability of MT cells. This could limit odor detection but increase discrimination ability. The proposed research is a highly integrated effort from two established investigators to understand the modulation of early olfactory processing at levels ranging from cells and circuits to single neurons in anesthetized and unanesthetized animals.