OLFACTORY BULB CIRCUIT ANALYSIS

这项研究的长期目标是更好地了解一个简单的皮层回路，嗅球的运作。 这些知识将提高对嗅觉辨别机制的理解，这在某些嗅觉功能障碍中可能是重要的;并将有助于理解一般的皮层功能。 具体的目标涉及测试的空间范围和突触机制的细胞之间的横向抑制与区域的球（肾小球），接收输入不同类型的嗅觉感觉神经元。这种输入似乎在嗅球的表面上创建了气味的空间图。 因此，通过增加球的弱激活区域和强激活区域之间的对比度，侧抑制应该增加大脑区分地图内活动位置的微小差异的能力。球的输出神经元之间的一种形式的侧抑制是由颗粒中间神经元介导的，并且是合理地理解的。 另一组通过肾小球周围（PG）中间神经元使用GABA和多巴胺作为递质的横向连接被认为是抑制性的，但了解甚少。 这些横向影响的空间范围和PG细胞的作用机制进行了研究。 将使用膜片钳电极记录维持在体外的嗅球薄片中的神经元的电活动，以响应对单个肾小球的刺激。神经递质机制将使用浴应用的药物，刺激或阻断递质的行动进行调查。在主嗅球和副嗅球切片中的记录结果将在计算机模型中进行模拟，以对完整系统的功能进行可测试的预测。

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.