DENDRITIC SIGNALING IN THE OLFACTORY BULB

嗅球中的树突信号传导

• 批准号: 6383073
• 负责人: GRAEME LOWE
• 金额: $ 21.34万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6383073
• 关键词: GABA receptor; NMDA receptors; action potentials; biological signal transduction; calcium; calcium flux; clathrate; dendrites; fluorimetry; gamma aminobutyrate; glutamate receptor; glutamates; laboratory rat; male; neural information processing; neural inhibition; neural transmission; neuroanatomy; neuroregulation; olfactory lobe; photostimulus; synapses; voltage /patch clamp

The mammalian olfactory system is unrivalled in its ability to detect, identify and discriminate an enormous variety of odor stimuli with exquisite sensitivity. What neural processing mechanisms underlie this remarkable feat? Odor information is relayed to the brain as spatially patterned activity in the glomerular layer of the olfactory bulb. The bulb transforms these patterns into the coordinated firing of ensembles of output neurons, the mitral cells. The long term objective of this research is to determine the dendritic and synaptic mechanisms that shape these firing patterns. Mitral cells radiate long secondary dendrites which are coupled, via reciprocal synapses, to granule cells. The deceptively simple structure of these dendrites belies their complex, multifunctional roles in signal processing. The aim of this project is to analyze the spatial organization of signaling in these dendrites. Our working model divides the dendrite into two dynamic domains: a proximal somatodendritic domain for temporal coding, and a distal dendritic domain for spatial coding. In the proximal domain, action potential timing is postulated to be controlled by: (i) integration of GABAergic input from reciprocal synapses, and (ii) modulation of intrinsic conductances by glutamate autoreceptors. In the distal domain, backpropagating action potentials activate calcium channels, triggering dendrodendritic transmission. It is postulated that spatial patterns of transmission depend on: (i) local modulation of action potentials, and (ii) differential distribution of calcium channels and AMPA or NMDA-type glutamate autoreceptors. We propose that calcium signaling is under dual feedback control: positive feedback amplification by NMDA receptors is balanced against negative feedback inhibition by GABA receptors. These mechanisms determine the spatiotemporal patterns of neurotransmission and electrical activity in the olfactory bulb that are central to odor information coding and processing. We analyze these mechanisms by combining brain slice patch-clamp, optical imaging, and laser photostimulation using caged compounds. This work has broad significance for understanding the control of dendritic transmission by patterns of electrical and calcium signaling, and may provide fundamental insights into the cellular bases of CNS pathologies involving the excitatory- inhibitory control of neural network activity, such as epilepsy.

哺乳动物的嗅觉系统在检测、识别和区分各种气味刺激方面具有无与伦比的能力，而且具有极高的敏感度。这一非凡成就背后的神经处理机制是什么？气味信息作为嗅球肾小球层的空间模式活动传递到大脑。灯泡将这些模式转换为输出神经元的集合--二尖瓣细胞--的协调放电。这项研究的长期目标是确定形成这些放电模式的树突和突触机制。二尖瓣细胞发出长的次级树突，这些树突通过相互突触与颗粒细胞相连。这些树突看似简单的结构掩盖了它们在信号处理中复杂、多功能的作用。这个项目的目的是分析这些树突中信号的空间组织。我们的工作模型将树突分为两个动态结构域：近端的躯体树突结构域用于时间编码，远端的树突结构域用于空间编码。在近端区域，动作电位的时序被认为是由：(I)来自相互突触的GABA能输入的整合，以及(Ii)谷氨酸自身受体对内源性电导的调节。在远端区域，反向传播动作电位激活钙通道，触发树突状传递。据推测，传递的空间模式取决于：(I)动作电位的局部调制，以及(Ii)钙通道和AMPA或NMDA型谷氨酸自体受体的不同分布。我们认为钙信号是受双反馈控制的：NMDA受体的正反馈放大和GABA受体的负反馈抑制是平衡的。这些机制决定了嗅球神经传递和电活动的时空模式，这是气味信息编码和处理的核心。我们通过结合脑片膜片钳、光学成像和使用笼状化合物的激光光刺激来分析这些机制。这项工作对于理解电和钙信号模式对树突传递的控制具有广泛的意义，并可能为癫痫等涉及神经网络活动的兴奋抑制控制的中枢神经系统病理的细胞学基础提供基本的见解。