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.
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