LOCAL CIRCUITS IN THE OLFACTORY BULB

嗅球是参与整合由鼻中的受体细胞转导的嗅觉感觉信息的主要脑区。 然而，对哺乳动物嗅球内在和突触反应的细胞基础知之甚少。 最近的研究表明嗅球神经元的内在和局部突触特性在气味辨别中起着积极的作用。 因此，本研究旨在探讨嗅球神经元内在特性和局部突触连接的细胞机制和功能。 嗅球中的主要神经元--二尖瓣细胞在嗅感受器细胞的兴奋性突触输入下去极化时产生动作电位簇。 这种反应的机制尚不清楚。在体内细胞内记录表明，当地延髓抑制输入往往占主导地位的输出的二尖瓣细胞在气味反应。 二尖瓣细胞抑制主要来自两个突触前树突的突触相互作用：释放谷氨酸的二尖瓣细胞次级树突和释放GABA的颗粒细胞树突。 当这两个树突相互作用时，发生复发性抑制，形成树-树突触。 我们已经证明，在哺乳动物嗅球的经常性和侧抑制发生通过这种相互树-树突触。 一系列的实验提出使用大鼠嗅球切片，以确定这些内在的和突触反应的细胞机制。 我们将首先集中在内在的反应，使用全细胞膜片钳记录从二尖瓣细胞，以确定在间歇性放电过程中的作用的Ca 2+内流。 接下来，将使用电压钳记录测试二尖瓣细胞对从其自身树突释放的谷氨酸的反应能力。 从耦合的二尖瓣和颗粒细胞和Ca 2+成像的双细胞内记录将被用来确定谷氨酸兴奋导致GABA从颗粒细胞树突的胞吐的机制。 最后，从二尖瓣细胞的电流钳记录将被用来定义在调节树突状细胞动作电位的反向传播的复发性和侧抑制的功能作用。 从这些实验的结果将提供一个更好的理解，如何内在的属性和局部突触反应的嗅球与感官输入编码嗅觉信息，并可能导致新的见解的一般原则，在中枢神经系统的感觉信息处理。

The olfactory bulb is the principal brain region involved in integrating olfactory sensory information transduced by receptor cells in the nose. However, relatively little is known about the cellular basis of intrinsic and synaptic responses in the mammalian olfactory bulb. Recent studies indicate that intrinsic and local synaptic properties of olfactory bulb neurons play an active role in odor discrimination. Therefore, the proposed research is designed to determine the cellular mechanism and function of intrinsic properties and local synaptic connections in olfactory bulb neurons. Mitral cells, the principal neurons in the olfactory bulb, generate clusters of action potentials when depolarizing by excitatory synaptic input from olfactory receptors cells. The mechanism underlying this response is unknown. In vivo intracellular recordings demonstrate that local bulbar inhibitory inputs often dominate the output of mitral cells during odor responses. Mitral cell inhibition arises predominately from the synaptic interaction of two presynaptic dendrites: mitral cell secondary dendrites that release glutamate and granule cell dendrites that release GABA. Recurrent inhibition occurs when these two dendrites interact, forming a dendrodendritic synapse. We have demonstrated that much of the recurrent and lateral inhibition in the mammalian olfactory bulb occurs through such reciprocal dendrodendritic synapses. A series of experiments are proposed using rat olfactory bulb slices to define the cellular mechanisms that underlie these intrinsic and synaptic responses. We will focus first on intrinsic responses using whole-cell patch-clamp recordings from mitral cells to determine the role of Ca2+ influx during intermittent firing. Next, the ability of mitral cells to respond to glutamate released from their own dendrites will be tested using voltage-clamp recordings. Dual intracellular recordings from coupled mitral and granule cells and Ca2+ imaging will be used to determine the mechanism by which glutamate excitation causes the exocytosis of GABA from granule cell dendrites. Finally, current-clamp recordings from mitral cells will be used to define the functional role of recurrent and lateral inhibition in regulating the backpropagation of dendritic action potentials. The results from these experiments will provide a better understanding of how intrinsic properties and local synaptic responses in the olfactory bulb are integrated with sensory inputs to encode olfactory information and may lead to new insights into general principles underlying sensory information processing in the CNS.