Mechanisms of Modular Neuronal Network Activation in the Olfactory Bulb

嗅球中模块化神经元网络激活的机制

• 批准号: 7637357
• 负责人: David Henry Gire
• 金额: $ 1.25万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-12-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7637357
• 关键词: Action Potentials; Brain; Breathing; Calcium; Cell physiology; Cells; Code; Data; Dendrites; Dendrodendritic Synapse; Disease; Dyes; Employee Strikes; Epilepsy; Esters; Functional disorder; Future; Generations; Goals; Human; Image; Imaging Techniques; In Vitro; Interneurons; Lead; Location; Mediating; Nature; Neurons; Neuropil; Odors; Olfactory Receptor Neurons; Output; Pattern; Phase; Play; Probability; Process; Rattus; Role; Sensory; Sensory Process; Signal Transduction; Slice; Stimulus; Synapses; System; Techniques; Testing; base; feeding; granule cell; in vivo; nervous system disorder; neuronal excitability; olfactory bulb; patch clamp; prevent; receptor; research study; response

DESCRIPTION (provided by applicant): Project Summary The main goal of the studies within this application is to define the role that a specific class of GABAergic neurons, called periglomerular (PG) cells, has in mediating information transfer in the olfactory bulb. The main hypothesis to be tested is that PG cells, through a feed-forward inhibitory mechanism onto output mitral cells, function to gate signals of different strengths, favoring strong signals over weak signals. Such a mechanism may be functionally important for enhancing differences between closely related odors. Each aim of this application will test a specific hypothesis that follows from this mechanism. The first aim will examine the general response profile of mitral cells, testing the specific hypothesis that "modules" of mitral cells engage in all-or-none responses to sensory input that occur simultaneously throughout the modular network. The second aim will then test the hypothesis that PG cells gate the generation of these mitral cell network responses. Experiments in aims 1 and 2 will primarily be done using electrophysiological techniques combined with pharmacological manipulations in rat in vitro olfactory bulb slices. The 3rd aim will test exactly how PG cells modulate mitral cell network responses, testing the specific hypothesis that PG cells inhibit mitral cells through a feed-forward mechanism. This hypothesis will be tested using calcium imaging of PG cells and electrophysiological recording of mitral cells in rat olfactory bulb slices. Taken together, the studies within this application will establish a role for PG cells in regulating information transfer through the first central relay of the olfactory system, the olfactory bulb. Relevance The studies described within this application will define mechanisms that inhibitory interneurons use to influence the excitability of neuronal circuits. Throughout the brain, dysfunction of this type of inhibition can lead to human disorders, perhaps the most notable being epilepsy. These studies will thus provide information that will aide in the understanding and treatment of neurological disorders, in addition to basic information about sensory processing.

描述（由申请人提供）：项目摘要本申请中的研究的主要目标是定义特定类别的GABA能神经元（称为Periglomerular（PG）细胞）的作用，它在介导嗅球中的信息传递中具有。要测试的主要假设是，PG细胞通过馈送前向抑制性机制到输出二尖瓣上，功能到具有不同强度的栅极信号，有利于强信号而不是弱信号。这种机制对于增强密切相关气味之间的差异可能在功能上很重要。该应用程序的每个目标都将检验此机制遵循的特定假设。第一个目的将检查二尖瓣细胞的一般响应曲线，检验以下特定假设：二尖瓣细胞的“模块”参与整个模块化网络中同时发生的全或不响应对感觉输入的响应。然后，第二个目标将检验PG细胞栅极构造这些二尖瓣网络响应的假设。 AIM 1和2中的实验将主要使用电生理技术与大鼠体外嗅球切片中的药理操作结合进行。第三AIM将准确测试PG细胞如何调节二尖瓣网络响应，并测试PG细胞通过馈送前馈机制抑制二尖瓣细胞的特定假设。该假设将使用PG细胞的钙成像和大鼠嗅球切片中二尖瓣细胞的电生理记录进行检验。综上所述，本应用中的研究将确定PG细胞在调节信息传输中通过嗅觉嗅球的第一个中央继电器的作用。相关性本应用程序中描述的研究将定义抑制性神经元用来影响神经元电路兴奋性的机制。在整个大脑中，这种抑制作用的功能障碍会导致人类疾病，也许是癫痫。因此，除了有关感官处理的基本信息外，这些研究还将提供有关神经系统疾病的理解和治疗的信息。