DENDRITIC SIGNALING IN THE OLFACTORY BULB

嗅球中的树突信号传导

• 批准号: 6523491
• 负责人: GRAEME LOWE
• 金额: $ 17.81万
• 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/6523491
• 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.

哺乳动物嗅觉系统的检测能力是无与伦比的，可以识别，识别和区分具有精致灵敏度的大量气味刺激。 哪些神经处理机制是这种非凡的壮举？ 在嗅球的肾小球层中，气味信息作为空间图案活性传递到大脑。 灯泡将这些模式转化为输出神经元（二尖瓣细胞）合奏的协调触发。 这项研究的长期目标是确定塑造这些射击模式的树突状和突触机制。 二尖瓣细胞辐射通过相互突触偶联到颗粒细胞的长期次生树突。 这些树突的看似简单的结构掩盖了它们在信号处理中的复杂，多功能的作用。 该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划分为两个动态域：用于时间编码的近端somatendritic域，以及用于空间编码的远端树突状域。 在近端域中，假定动作电位时机由以下操作控制：（i）从相互突触中积分GABA能输入，以及（ii）通过谷氨酸自身受体对内在电导的调节。 在远端结构域中，反向传播作用电位激活钙通道，从而触发树突状传播。 据推测，传输的空间模式取决于：（i）作用电位的局部调节，以及（ii）钙通道和AMPA或NMDA型谷氨酸自身受体受体的差分分布。 我们建议钙信号在双重反馈控制下：NMDA受体的正反馈扩增与GABA受体的负反馈抑制平衡。 这些机制决定了嗅球中神经传递和电活动的时空模式，这是气味信息编码和加工的核心。 我们通过使用笼子化合物结合脑切片片钳，光学成像和激光光刺激来分析这些机制。 这项工作对于通过电信号和钙信号模式来理解对树突状传播的控制具有广泛的意义，并且可以为CNS病理的细胞碱基提供涉及神经网络活性的兴奋性抑制性控制（例如癫痫病）的基本见解。