Circuit functions of fast-spiking interneurons in the main olfactory bulb

项目摘要/摘要 嗅觉系统对哺乳动物的行为和生存的几个方面至关重要，包括人类。这个 嗅球是嗅觉系统的第一个处理站，是一种特殊的模型系统 对于神经编码的研究，能够在紧凑和良好的 有组织的结构。因此，了解嗅球内的局部电路计算将提供关键的洞察力 大脑功能的基本原理。嗅球内突触抑制的广泛扰动 显著扰乱投射二尖瓣/簇状细胞同步和嗅觉引导行为，强调 抑制性中间神经元在局部电路计算中的中心作用。与大脑的其他区域形成对比的是 然而，由于大脑皮层和海马区，基本了解了不同的抑制性中间神经元是如何 在嗅球内，对神经编码的具体支持仍然是难以捉摸的，对如何 单一突触的相互作用尤其有助于精确调节二尖瓣/簇状细胞的棘波时序 缺乏。为了加深对嗅球局部电路计算和神经编码的理解，这个项目 因此将直接研究二尖瓣/簇生细胞和高度保守的 但是，使用急性小鼠脑片的全细胞对记录，对一类快速放电的中间神经元研究不足 结合药理学、形态重建、免疫染色和模拟。调查将会 具体解决三个目标：1)确定快速放电中间神经元如何调节二尖瓣/簇状细胞尖峰 计时，2)决定树突计算如何支持快速尖峰的中间神经元功能，以及3)决定如何 快速放电的中间神经元信号与神经活动相适应。

PROJECT SUMMARY/ABSTRACT The olfactory system is critical to several aspects of behavior and survival in mammals, including humans. The olfactory bulb is the first processing station of the olfactory system and constitutes an exceptional model system for the study of neural coding, capable of encoding a highly complex sensory space within a compact and well- organized structure. Understanding local circuit computation within the olfactory bulb will thus provide key insight into fundamental principles of brain function. Broad perturbation of synaptic inhibition within the olfactory bulb significantly disrupts projection mitral/tufted cell synchronization and olfactory-guided behavior, underscoring a central role of inhibitory interneurons in local circuit computation. In contrast to other regions of the brain such as neocortex and hippocampus, however, fundamental understanding of how the diverse inhibitory interneurons within the olfactory bulb specifically support neural coding has remained elusive, with detailed knowledge of how unitary synaptic interactions contribute to the precise regulation of mitral/tufted cell spike timing in particular lacking. To advance understanding of local circuit computation and neural coding in the olfactory bulb, this project will therefore directly examine unitary synaptic interactions between mitral/tufted cells and a highly-conserved but understudied class of fast-spiking interneurons, using whole-cell pair recordings in acute mouse brain slices together with pharmacology, morphological reconstruction, immunostaining, and simulations. Investigation will specifically address three aims: 1) determine how fast-spiking interneurons regulate mitral/tufted cell spike timing, 2) determine how dendritic computation supports fast-spiking interneuron function, and 3) determine how fast-spiking interneuron signaling adapts with neural activity.