OLFACTORY BULB CIRCUIT ANALYSIS

这项研究的长期目标是更好地理解一个简单的皮层回路——嗅球的运作。这一知识将提高对嗅觉辨别机制的理解，在某些嗅觉功能障碍中可能很重要；这将有助于理解大脑皮层的一般功能。具体目的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）区域相关的细胞间横向抑制的空间范围和突触机制。这种输入似乎在嗅球表面创造了一个气味的空间地图。侧抑制，通过增加弱和强激活区域之间的对比，因此应该增加大脑在该地图中区分活动位置的微小差异的能力。一种形式的横向抑制之间的输出神经元的球是由颗粒中间神经元介导，并相当好地理解。另一组侧向连接，通过肾小球周围（PG）中间神经元使用GABA和多巴胺作为递质，被认为是抑制性的，但知之甚少。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。利用膜片钳电极记录体外保存的嗅球薄片神经元的电活动，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。主要和附属嗅球切片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.