Mechanisms of Modular Neuronal Network Activation in the Olfactory Bulb

本项目研究的主要目标是确定一类特定的gaba能神经元，称为肾小球周围细胞（PG），在嗅球中介导信息传递中的作用。要验证的主要假设是，PG细胞通过对二尖瓣输出细胞的前馈抑制机制，对不同强度的信号进行门控，偏爱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具有重要的功能。此应用程序的每个目标将测试从该机制中遵循的特定假设。第一个目标将检查二尖瓣细胞的一般反应概况，测试二尖瓣细胞的“模块”参与对整个模块网络同时发生的感觉输入的全或无反应的特定假设。第二个目标将测试PG细胞限制二尖瓣细胞网络反应的产生的假设。目的1和目的2的实验将主要使用电生理技术结合药理操作在大鼠离体嗅球切片上进行。第三个目标将测试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。这一假设将通过大鼠嗅球切片中PG细胞的钙成像和二尖瓣细胞的电生理记录进行验证。综上所述，本应用中的研究将确定PG细胞在通过嗅觉系统的第一个中央继电器嗅球调节信息传递中的作用。本应用程序中描述的研究将定义抑制中间神经元用来影响神经元回路兴奋性的机制。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，最显著的可能是癫痫。因此，这些研究除了提供有关感觉处理的基本信息外，还将提供有助于理解和治疗神经系统疾病的信息。

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.