DENDRITIC SIGNALING IN THE OLFACTORY BULB

哺乳动物的嗅觉系统在探测、识别和区分各种气味刺激的能力上是无与伦比的。是什么神经处理机制导致了这一惊人的成就？气味信息在嗅球的肾小球层以空间模式活动的形式传递给大脑。灯泡将这些模式转化为输出神经元（二尖瓣细胞）的协同放电。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。二尖瓣细胞放射出长长的次级树突，它们通过相互突触与颗粒细胞偶联。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域：用于时间编码的近端体树突域和用于空间编码的远端树突域。在近端区域，动作电位的时间被认为是由：(i)来自互反突触的gaba能输入的整合，以及（ii）谷氨酸自受体对内在电导的调节。在远端区域，反向传播的动作电位激活钙通道，触发树突传递。据推测，传递的空间模式取决于：(i)局部动作电位的调节，以及（ii）钙通道和AMPA或nmda型谷氨酸自受体的差异分布。我们认为钙信号受双重反馈控制：NMDA受体的正反馈放大与GABA受体的负反馈抑制相互平衡。这些机制决定了嗅球中神经传递和电活动的时空模式，这些模式是气味信息编码和处理的核心。我们结合脑切片膜片钳、光学成像和笼状化合物的激光光刺激来分析这些机制。这项工作对于理解通过电和钙信号模式控制树突传递具有广泛意义，并可能为涉及神经网络活动兴奋性抑制控制的中枢神经系统病理（如癫痫）的细胞基础提供基本见解。

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.