LOCAL CIRCUITS IN THE OLFACTORY BULB

嗅球是大脑中主要的区域，参与整合由鼻子中的受体细胞传递的嗅觉感觉信息。然而，对哺乳动物嗅球内禀和突触反应的细胞基础知之甚少。近年来的研究表明，嗅球神经元的内在和局部突触特性在气味识别中起着积极的作用。因此，本研究旨在确定嗅球神经元内在特性和局部突触连接的细胞机制和功能。二尖瓣细胞是嗅球中的主要神经元，当嗅觉受体细胞的兴奋性突触输入使其去极化时，会产生动作电位簇。这种反应背后的机制尚不清楚。体内细胞内记录表明，在气味反应过程中，局部球抑制输入通常主导二尖瓣细胞的输出。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形成树突突触时，会发生反复抑制。我们已经证明，哺乳动物嗅球中的许多反复抑制和侧抑制都是通过这种互惠的树突突触发生的。一系列的实验提出使用大鼠嗅球切片来定义这些内在和突触反应背后的细胞机制。我们将首先关注使用全细胞膜片钳记录二尖瓣细胞的内在反应，以确定间歇性放电期间Ca2+内流的作用。接下来，二尖瓣细胞对自身树突释放的谷氨酸的反应能力将通过电压钳记录进行测试。二尖瓣和颗粒细胞的双重细胞内记录和Ca2+成像将用于确定谷氨酸兴奋导致颗粒细胞树突分泌GABA的机制。最后，二尖瓣细胞的电流钳记录将用于确定复发抑制和侧抑制在调节树突动作电位反向传播中的功能作用。这些实验的结果将更好地理解嗅球的内在特性和局部突触反应如何与感觉输入相结合以编码嗅觉信息，并可能导致对中枢神经系统中感觉信息处理的一般原理的新见解。

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.