Synaptic plasticity in the mammalian olfactory bulb

描述(申请人提供)：半个世纪以来，哺乳动物大脑中的突触可塑性一直是学习和记忆研究的主导范式。嗅球一直被认为是某些形式的嗅觉记忆的场所，而二尖瓣颗粒细胞的相互突触是嗅球中一个突出的突触。二尖瓣-颗粒突触值得研究有三个原因。首先，它介导了嗅球的侧向抑制和相互抑制，形成了嗅球输出神经元对气味刺激的反应。其次，兴奋和抑制的突触动力学的相互作用可能会对刺激模式产生复杂的反应。第三，这种突触的相互排列为突触前和突触后过程的直接相互作用提供了机会。因此，二尖瓣颗粒细胞相互突触是研究哺乳动物大脑学习的电路和机制的极好场所。 在嗅球切片制备过程中，将从二尖瓣和颗粒细胞中进行全细胞记录。这些研究将(1)表征与体内气味采样相对应的时间进程中兴奋和抑制方向的短期和长期可塑性，以及(2)使用药物操作、钙缓冲和突变小鼠来表征可塑性的机制。

DESCRIPTION (provided by applicant): For half a century, synaptic plasticity in the mammalian brain has been the leading paradigm for the study of learning and memory. The olfactory bulb has been supposed to be a site for certain forms of olfactory memories, and the mitral-granule cell reciprocal synapse is a prominent synapse in the bulb. The mitral-granule synapse is worthy of study for three reasons. First, it mediates lateral and reciprocal inhibition in the olfactory bulb, which shape the responses of the output neurons of the olfactory bulb to odor stimuli. Second, the interplay of synaptic dynamics of excitation and inhibition may produce a complex response to patterns of stimuli. Third, the reciprocal arrangement of this synapse presents an opportunity for the direct interaction of pre- and postsynaptic processes. Therefore, the mitral-granule cell reciprocal synapse is an excellent site at which to study the circuits and mechanisms that underlie learning in the mammalian brain. Whole-cell recordings will be made from mitral and granule cells in the olfactory bulb slice preparation. These studies will (1) characterize short- and longterm plasticity in both the excitatory and inhibitory directions over time courses corresponding to odor sampling in vivo, and (2) use pharmacological manipulations, calcium buffers and mutant mice to characterize the mechanisms of the plasticity.