OLFACTORY BULB CIRCUIT ANALYSIS

这项研究的长期目标是更好地了解简单的大脑皮层回路--嗅球的运作。这一知识将促进对嗅觉辨别机制的理解，这在一些嗅觉功能障碍中可能是重要的；并将有助于对大脑皮层功能的总体理解。具体目标包括测试与接受不同类型嗅觉感觉神经元输入的球(肾小球)区域相关的细胞之间的侧向抑制的空间范围和突触机制。这一输入似乎创建了嗅球表面气味的空间地图。侧向抑制，通过增加灯泡的弱激活区域和强激活区域之间的对比度，因此应该会增强大脑区分该图中活动位置的微小差异的能力。一种形式的球输出神经元之间的侧抑制是由颗粒中间神经元介导的，这是相当好的理解。另一组侧向连接是通过球周(PG)间神经元，使用GABA和多巴胺作为递质，被认为是抑制性的，但人们对此知之甚少。这些横向影响的空间范围和PG细胞的作用机制在这里进行了研究。在体外保存的嗅球薄片中，神经元的电活动将使用膜片钳电极记录下来，以响应单个肾小球的刺激。神经递质机制将使用刺激或阻断递质作用的沐浴药物进行研究。主嗅球切片和副嗅球切片的记录结果将在计算机模型中模拟，以对完整系统的功能做出可测试的预测。

The long-term goals of this research are to understand better the operation of a simple cortical circuit, the olfactory bulb. This knowledge will improve understanding of the mechanisms of olfactory discrimination, potentially important in some olfactory dysfunctions; and will contribute to understanding of cortex function in general. The specific aims involve tests of spatial extent and synaptic mechanisms for lateral inhibition between cells associated with regions of the bulb (glomeruli) that receive input from different types of olfactory sensory neurons. This input appears to create a spatial map of odors across the surface of the olfactory bulb. Lateral inhibition, by increasing contrast between weakly and strongly activated regions of the bulb, should therefore increase the brain's ability to distinguish between small differences in the location of activity within that map. One form of lateral inhibition between output neurons of the bulb is mediated by granule interneurons and is reasonably well understood. Another set of lateral connections, via periglomerular (PG) interneurons using GABA and dopamine as transmitters is thought to be inhibitory but is poorly understood. The spatial extent of these lateral influences and the mechanisms of PG cell action are investigated here. The electrical activity of neurons in thin slices of olfactory bulb maintained in vitro will be recorded using patch-clamp electrodes, in response to stimulation of individual glomeruli. Neurotransmitter mechanisms will be investigated using bath-applied drugs that stimulate or block transmitter action. Results of the recordings in main and accessory olfactory bulbs slices will be simulated in computer models to make testable predictions about the function of the intact systems.