Optical Studies of Neuron Activity and Organization

Yale University, New Haven CT

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Abstract

The long term goal of the proposed experiments is to understand how animals perceive odors. The experiments in the present proposal are designed to improve our understanding of the function and role of the olfactory bulb in this process. Maps of the input to the bulb are available from optical recordings of calcium and pH signals. Here we propose to use optical recording methods to monitor the activity of postsynaptic cells in the olfactory bulb in an in vivo mouse preparation. First, we plan to use bulk injection of calcium dyes and 2-photon microscopy to simultaneously monitor the activity of many (tens) of individual neurons in response to odorant presentations. We plan to make these recordings from both juxtaglomerular neurons that surround the glomeruli and from mitral cells which provide the output of the olfactory bulb. The ability to record from many neurons simultaneously should greatly improve our understanding of olfactory bulb function. Second, we propose to use genetically encoded voltage-sensitive proteins (FP-voltage sensors) expressed in the mitral/tufted cells to monitor the output of the bulb in response to odor presentations. A comparison of the output map with the input map would provide a strong statement about the function of the olfactory bulb in odorant processing. The FP-voltage sensors that work well in Xenopus oocytes have been only marginally successful when applied to mammalian preparations. We propose modifications to improve the FP-voltage sensor signal-tonoise ratio in mammalian cells. These improvements would facilitate their use in any cell type in the mammalian brain and thereby contribute to the understanding of many aspects of brain function. The experiments proposed here would further our basic understanding of olfactory processing. In the long term this understanding will provide opportunities for alleviating failures of processing of this important sensory input.