Local circuits in the olfactory bulb

嗅球中的局部电路

• 批准号: 10188484
• 负责人: Ben W Strowbridge
• 金额: $ 34.21万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188484
• 关键词: Action Potentials; Acute; Address; Affect; Alzheimer' s Disease; Area; Biological; Brain; Brain region; Cell physiology; Cells; Code; Cognitive deficits; Complex; Diffuse; Disease; Distal; Electrodes; Electrophysiology (science); Environment; Equilibrium; Excitatory Postsynaptic Potentials; Functional disorder; Funding; Glutamates; Goals; Imaging Techniques; Impairment; In Vitro; Individual; Interneurons; Kinetics; Lead; Logic; Mediating; Methods; Modality; Molecular; Neurodegenerative Disorders; Neurons; Neurosciences; Odors; Olfactory Cortex; Olfactory Pathways; Onset of illness; Output; Parkinson Disease; Pathway interactions; Pattern; Photometry; Population; Positioning Attribute; Preparation; Process; Receptor Cell; Research; Rodent; Role; Schizophrenia; Sensory; Shapes; Slice; Smell Perception; Stimulus; Synapses; Synaptic plasticity; Testing; Time; Work; autism spectrum disorder; base; brain cell; detector; experimental study; granule cell; imaging modality; insight; mitral cell; nervous system disorder; neural circuit; olfactory bulb; olfactory stimulus; optical imaging; programs; public health relevance; receptor; recruit; relating to nervous system; response; sensory input; sensory stimulus; spatiotemporal; two-photon; voltage

Project Summary A central question in neuroscience is how sensory stimuli in the environment are represented. The olfactory system is an attractive sensory modality to approach this question since the major excitatory pathways that connect receptor neurons, second-order mitral cells in the olfactory bulb, and tertiary neurons in olfactory cortex and well understood. However, intracellular recordings demonstrate that neural representations of odors in second-order neurons (mitral and tufted cells) do not result exclusively from feedforward input from receptor cells. Instead, the output of the olfactory bulb results from complex interactions between excitatory and inhibitory circuits. Relatively little is known about the neural circuits that generate inhibition onto principal cells. The present proposal uses rodent brain slice recording methods to determine how local circuit pathways excite GABAergic olfactory bulb interneurons, inhibiting and shaping firing patterns in principal cells. Using both whole-cell intracellular recording and live 2-photon imaging methods, we will determine how the key synaptic pathways that enable sensory input to excite granule cells function and how they recruit intrinsic currents within granule cells. The proposal also will determine how inhibitory synaptic input to granule cells functions to modulation action potential discharges. Finally, the proposed work also will determine the functional role of a recently discovered form of long-term synaptic plasticity apparent in one class of these inputs. Defining the cellular mechanisms that generate sensory-evoked inhibition in the olfactory bulb, the overall focus of this proposal, is critical to understand how biological information is represented in the brain. The proposed studies also are significant as they represent an important step toward understanding the specific deficits in many major neurodegenerative diseases in which olfactory function is affected. In many of these diseases, sensory impairments occur early in the disease onset. Insights into the specific olfactory mechanisms affected in these diseases may lead to directly testable hypotheses regarding analogous mechanisms in the cortical areas responsible for the cognitive deficits commonly associated with neurodegenerative disorders.

项目摘要 神经科学的一个中心问题是环境中的感官刺激是如何表现的。嗅 系统是一个有吸引力的感觉方式来解决这个问题，因为主要的兴奋性途径， 连接感受神经元、嗅球二级僧帽细胞和嗅球三级神经元 皮质和良好的理解。然而，细胞内记录表明， 二级神经元（二尖瓣和簇状细胞）中的气味并不完全来自前馈输入， 受体细胞相反，嗅球的输出是由兴奋性神经元之间复杂的相互作用引起的。 和抑制回路相对而言，我们对产生抑制的神经回路知之甚少。 主要细胞目前的建议使用啮齿动物脑切片记录方法来确定如何局部 电路通路兴奋GABA能嗅球中间神经元，抑制和塑造放电模式， 主要细胞使用全细胞细胞内记录和活双光子成像方法，我们将 确定关键的突触通路如何使感觉输入兴奋颗粒细胞的功能，以及如何 它们在颗粒细胞内募集内在电流。该提案还将确定抑制性突触 输入到颗粒细胞的功能是调节动作电位放电。最后，建议的工作还 将确定最近发现的一种长期突触可塑性的功能作用， 这些输入的一个类别。定义产生感觉诱发抑制的细胞机制， 嗅球，这个建议的整体重点，是至关重要的，以了解生物信息是如何 在大脑中表现出来。拟议的研究也很重要，因为它们代表了一个重要步骤， 为了了解在许多主要的神经退行性疾病，其中嗅觉的具体缺陷， 功能受到影响。在许多这些疾病中，感觉障碍发生在疾病发作的早期。 深入了解这些疾病中受影响的特定嗅觉机制可能会直接测试 关于负责认知缺陷的皮质区中的类似机制的假设 通常与神经退行性疾病有关。