LOCAL CIRCUITS IN THE OLFACTORY BULB

嗅球是参与整合嗅觉信息的主要大脑区域，这些信息由鼻子中的感受器细胞传递。然而，对哺乳动物嗅球的固有反应和突触反应的细胞基础知之甚少。最近的研究表明，嗅球神经元的固有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的固有特性和局部突触连接的细胞机制和功能。二尖瓣细胞是嗅球的主要神经元，当嗅觉感受器细胞的兴奋性突触输入去极化时，二尖瓣细胞产生一连串的动作电位。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，局部球抑制输入经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，就会出现反复的抑制。我们已经证明，哺乳动物嗅球中的许多反复和侧向抑制都是通过这种相互作用的树-树突触发生的。建议使用大鼠嗅球切片进行一系列实验，以确定这些内在和突触反应背后的细胞机制。我们将首先使用来自二尖瓣细胞的全细胞膜片钳记录来研究内源性反应，以确定钙离子内流在间歇性放电过程中的作用。接下来，将使用电压钳记录来测试二尖瓣细胞对自身树突释放的谷氨酸的反应能力。二尖瓣和颗粒细胞的双重细胞内记录和钙成像将被用来确定谷氨酸刺激引起颗粒细胞树突的GABA胞吐的机制。最后，二尖瓣细胞的电流钳记录将被用来确定反复抑制和侧向抑制在调节树突状细胞动作电位反向传播中的功能作用。这些实验的结果将提供更好的了解嗅球的内在特性和局部突触反应是如何与感觉输入整合以编码嗅觉信息的，并可能导致对中枢神经系统感觉信息处理的一般原理的新的见解。

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.