Modulation of Glomerular Function

肾小球功能的调节

• 批准号: 8793691
• 负责人: Michael Thomas Shipley
• 金额: $ 42.88万
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8793691
• 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; neuroregulation; olfactory bulb; olfactory bulb glomeruli; operation; postsynaptic; presynaptic; public health relevance; raphe nuclei; receptor; relating to nervous system; research study; response; sensory input; 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是由嗅球（OB）Glomeruli中的神经回路处理的。该电路是由来自神经调节中心的离心输入的目标。通过二尖瓣/簇状（MT）细胞的OB输出显示出明显的调节，对清醒动物中的感觉反应进行了显着调节。知道这些气味信息处理的最早阶段是如何调制的，对于完全理解嗅觉系统功能至关重要。该项目将首次研究乙酰胆碱（ACH）和5-羟色胺（5HT）如何调节肾小球电路中的感觉处理。这项研究以我们对这些电路的理解及其在塑造OB产出中的重要性的最新进展为基础。该项目将整合来自OB切片的信息，并麻醉和清醒的头部固定小鼠。这种多维方法旨在将肾小球电路的调节与特定神经调节系统的激活联系起来 - 对角条带的胆碱能输入和来自Raphe Nuclei的血清素能输入。我们的工作假设是，ACH和5HT差异调节肾小球处理以塑造突触前和后抑制后的抑制以及MT细胞兴奋性。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，但会增加歧视能力。拟议的研究是两名知名研究人员的高度综合努力，以了解从细胞和电路到麻醉和未消除动物的单个神经元等水平的早期嗅觉加工的调节。