Modulation of Glomerular Function

肾小球功能的调节

• 批准号: 8413776
• 负责人: Michael Thomas Shipley
• 金额: $ 41.15万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413776
• 关键词: Acetylcholine; Agonist; Alzheimer' s Disease; Animals; Attention; Brain; Cells; Complex; Data; Detection; Discrimination; Disease; Dissection; Dorsal; Equilibrium; Frequencies; Functional disorder; Head; Health; Human; In Vitro; Knowledge; Lead; Learning; Link; Mental Depression; Moods; Mus; Muscarinic Acetylcholine Receptor; Neurons; Nicotinic Receptors; Odors; Olfactory Pathways; Output; Pathway interactions; Perception; Play; Population; Process; Property; Research; Research Personnel; Role; Schizophrenia; Sensory; Sensory Process; Serotonin; Shapes; Signal Transduction; Slice; Staging; Stimulus; Synapses; System; Time; Tweens; Visual; Whole-Cell Recordings; Work; awake; basal forebrain; base; cholinergic; gamma-Aminobutyric Acid; gaze; glomerular function; granule cell; improved; in vivo; information processing; inhibitory neuron; millisecond; neural circuit; olfactory bulb; operation; postsynaptic; presynaptic; public health relevance; raphe nuclei; receptor; relating to nervous system; research study; response; sensory system; tool; vigilance

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.

描述（由申请人提供）：嗅觉系统的感觉输入最初由嗅球（OB）肾小球的神经回路处理。这个电路是由神经调节中心的离心输入所瞄准的。通过二尖瓣/簇状（MT）细胞输出OB显示了清醒动物的感觉反应的显著调节。了解这些气味信息处理的早期阶段是如何被调节的，对于充分理解嗅觉系统的功能至关重要。该项目将首次研究乙酰胆碱（ACh）和血清素（5HT）如何调节肾小球回路中的感觉加工。这项研究建立在我们对这些电路的理解以及它们在塑造OB输出中的重要性的最新进展之上。该项目将整合来自OB切片和麻醉和清醒头部固定小鼠的信息。这种多维度的方法旨在将肾小球回路的调节与特定神经调节系统的激活联系起来——来自对角线带的胆碱能输入和中隔核的血清素能输入。我们的工作假设是ACh和5HT不同地调节肾小球加工，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调节减少了感觉输入的影响，同时增加了MT细胞的兴奋性。这可能会限制气味检测，但增加辨别能力。拟议的研究是两位知名研究人员的高度整合的努力，旨在了解麻醉和未麻醉动物从细胞、回路到单个神经元的早期嗅觉处理的调节。