Feedforward inhibition in the olfactory bulb: Cellular basis of differential mitr

嗅球的前馈抑制：微分 mitr 的细胞基础

• 批准号: 9093762
• 负责人: Richard Todd Pressler
• 金额: $ 15.85万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093762
• 关键词: Action Potentials; Acute; Address; Affect; Axon; Brain; Brain region; Cell physiology; Cells; Characteristics; Defect; Dendrites; Distal; Electrophysiology (science); Generations; Golgi Apparatus; Health; Hippocampus (Brain); Image; In Vitro; Interneurons; Laboratories; Life; Location; Mediating; Morphology; Myoepithelial cell; Nasal Epithelium; Neuraxis; Neurons; Neurosciences; Olfactory Cortex; Olfactory Receptor Neurons; Output; Pathology processes; Pattern; Play; Preparation; Presynaptic Terminals; Process; Property; Publications; Research; Resolution; Rodent; Role; Route; Slice; Smell Perception; Staining method; Stains; Structure; Sum; Synapses; Time; Work; base; granule cell; horizontal cell; mitral cell; neocortical; neuronal cell body; novel; olfactory bulb; olfactory sensory neurons; patch clamp; piriform cortex; research study; respiratory; response; sensory input; two-photon

DESCRIPTION (provided by applicant): The olfactory bulb performs a critical role in encoding olfactory information and routing it to downstream brain regions. This proposal defines an experimental plan to determine the subtypes of local interneurons that provide inhibitory input to mitral cells, one of the main classes of output cells in the olfactory bulb. These inhibitory circuts govern how the circuit is activated and sculpt mitral cell activity. I will first determine the speific subtypes of local interneurons that have axon terminals in layers containing mitral cell processes. There are several relatively unexplored interneuron subtypes in the olfactory bulb that could synapse onto mitral cells, in addition to commonly studied granule cells. My preliminary studies have suggested that one of these, oriented horizontal cells, monosynaptically inhibits mitral cells. Using whole-cell patch clamp electrophysiology and live 2-photon imaging in acute rodent brain slices, I will define the morphological and electrophysiological properties of interneurons with axonal ramifications near the mitral cell layer. Using visualized paired recordings, I will then determine which of these interneuron subtypes actually inhibits mitral cells and define the functional consequences of this inhibition. Next, I will trigger excitation onto these local interneurons by stimulating olfactory sensory neuron axons and determine whether horizontal (and related) classes of interneurons are activated by relatively few glomerular columns (like mitral and tufted cells are) or, instead, integrate synaptic input widely from multiple input glomeruli. Finally, I will also use an in vitro combined olfactory bulb/piriform cortex slice preparation to determine if these interneurons receive centrifugal input from olfactory cortex. Using these strategies, I will determine the set o olfactory bulb circuits that inhibit mitral cells and how this inhibition affects mitral cell functon.

描述（由申请人提供）：嗅球在编码嗅觉信息并将其路由到下游大脑区域方面发挥着关键作用。该提案定义了一个实验计划，以确定向二尖瓣细胞提供抑制输入的局部中间神经元的亚型，二尖瓣细胞是嗅球中输出细胞的主要类别之一。这些抑制性电路控制着电路的激活方式并塑造二尖瓣细胞的活动。我将首先确定在包含二尖瓣细胞突起的层中具有轴突末端的局部中间神经元的特定亚型。除了通常研究的颗粒细胞之外，嗅球中还有几种相对未开发的中间神经元亚型可以突触到二尖瓣细胞。我的初步研究表明，其中一种定向水平细胞单突触抑制二尖瓣细胞。在急性啮齿动物脑切片中使用全细胞膜片钳电生理学和活体双光子成像，我将定义二尖瓣细胞层附近具有轴突分支的中间神经元的形态和电生理学特性。然后，我将使用可视化的配对记录来确定哪些中间神经元亚型实际上抑制二尖瓣细胞，并定义这种抑制的功能后果。接下来，我将通过刺激嗅觉感觉神经元轴突来触发这些局部中间神经元的兴奋，并确定水平（和相关）类别的中间神经元是否被相对较少的肾小球柱（如二尖瓣和簇状细胞）激活，或者相反，广泛整合来自多个输入肾小球的突触输入。最后，我还将使用体外 结合嗅球/梨状皮层切片制备以确定这些中间神经元是否接收来自嗅觉皮层的离心输入。使用这些策略，我将确定抑制二尖瓣细胞的嗅球电路组以及这种抑制如何影响二尖瓣细胞功能。