Mechanisms of Modular Neuronal Network Activation in the Olfactory Bulb

描述（由申请人提供）：项目概述本申请中研究的主要目标是确定一类特定的GABA能神经元（称为肾小球周围（PG）细胞）在嗅球中介导信息传递的作用。待检验的主要假设是PG细胞通过对输出二尖瓣细胞的前馈抑制机制，起到门控不同强度的信号的作用，从而有利于强信号而不是弱信号。这种机制对于增强密切相关的气味之间的差异可能在功能上是重要的。本应用程序的每个目标都将测试从该机制得出的特定假设。第一个目标将检查二尖瓣细胞的一般响应曲线，测试特定的假设，即二尖瓣细胞的“模块”对在整个模块化网络中同时发生的感觉输入进行全或无响应。第二个目标将测试PG细胞门控这些二尖瓣细胞网络反应的产生的假设。目的1和2的实验将主要使用电生理技术结合药理学操作在大鼠离体嗅球切片中进行。第三个目标将准确测试PG细胞如何调节二尖瓣细胞网络反应，测试PG细胞通过前馈机制抑制二尖瓣细胞的特定假设。将使用PG细胞的钙成像和大鼠嗅球切片中的二尖瓣细胞的电生理记录来检验这一假设。总之，本申请中的研究将确定PG细胞在通过嗅觉系统的第一个中央中继（嗅球）调节信息传递中的作用。相关性本申请中描述的研究将定义抑制性中间神经元用于影响神经元回路的兴奋性的机制。在整个大脑中，这种类型的抑制功能障碍可能导致人类疾病，也许最值得注意的是癫痫。因此，这些研究将提供信息，将有助于理解和治疗神经系统疾病，除了有关感觉处理的基本信息。

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.