Differential odor-response and central-projection patterns of mitral and tufted c

描述（由申请人提供）：平行处理是不同感觉系统的共同原则。大脑倾向于将感觉刺激的不同方面编码为单独的投射路径，以进行针对特定特征的优化处理。虽然平行通路在其他感觉模式中得到了很好的研究，但嗅觉信号是如何通过类似的平行处理电路传递到高阶中枢的，目前还不清楚。在本次授权中，我建议通过关注嗅球中的两种主要类型的投射神经元，二尖瓣细胞和簇状细胞来探索这个问题。虽然早期对神经元形态的分析表明，它们可能代表两种不同的气味处理途径，但它们的功能差异尚未得到很好的表征。这主要是由于在不知道感兴趣的神经元是否接受来自共同或不同肾小球的嗅觉输入的情况下，很难比较气味反应特性。此外，尚不清楚这些细胞是否有不同的轴突投射到嗅结节和梨状皮质。为了解决这两个问题，我将利用我最近开发的方法，将右旋糖酐染料局部电穿孔和体内双光子钙成像结合起来，同时实现神经回路的追踪和细胞功能的成像。我们将对共享共同肾小球输入的二尖瓣细胞和簇状细胞的气味响应谱进行系统的比较分析，以探索它们在编码和处理不同气味特征方面的不同参与方式。基于我目前的初步数据，我将进一步验证二尖瓣细胞和簇状细胞对轴突终止场表现出不同偏好的假设。通过这两个系列的实验，我希望最终从功能和电路的角度建立，二尖瓣细胞和簇状细胞确实构成了两条并行的处理途径，处理不同的气味信息。

DESCRIPTION (provided by applicant): Parallel processing is a common principle across different sensory systems. The brain tends to encode different aspects of a sensory stimulus into separate projection pathways for carrying out unique processing optimized for dedicated features. Though parallel pathways are well studied in other sensory modalities, it remains unclear how olfactory signals are transmitted to high-order centers through similar parallel-processing circuits. In this grant, I propose to explore this issue by focusing on the two major types of projection neurons in the olfactory bulb, the mitral and tufted cells. While early analyses of neuronal morphology suggest that they may represent two separate pathways for odor processing, their functional distinctions have not yet been well characterized. This is mainly due to the fact that it is difficult to compare the odor-response properties without knowing whether interested neurons receive olfactory inputs from common or different glomeruli. Furthermore, it is not clear whether these cells have different axonal projections into the olfactory tubercle and piriform cortex. To address these two questions, I will take advantage of my recently developed approach, which combines dextran-dye local electroporation and in vivo two-photon calcium imaging to achieve simultaneous tracing of neural circuits and imaging of cellular functions. A systematic comparative analysis will be carried out on the odor response profiles of mitral and tufted cells sharing a common glomerular input, in search for insights into how they are differently involved in coding and processing different odor features. Based on my current preliminary data, I will further test the hypothesis that mitral and tufted cells display different preferences of their axonal termination fields. With these two series of experiments, I expect to ultimately establish, from both the functional and circuitry points of view, that mitral and tufted cells indeed constitute two parallel processing pathways handling different sets of odor information. Public Health Relevance: All sensory systems essentially provide a parallel interface between our brain and external environment. Neural mechanisms underlying the parallel processing of sensory inputs have already been well studied in the visual and auditory systems. However, for the sense of smell, which contributes critically to our daily life quality, it remains so far poorly understood how such parallel signal-processing mechanisms are implemented in this system, especially at the neuronal-circuit level. I here propose a series of experiments to test the hypothesis that the two major types of principal neurons in the olfactory bulb, the mitral and tufted cells, display quite different odor response profiles and central axonal projection patterns. Such differences enable these neurons to function as the backbone in two parallel odor-processing pathways, which are involved in processing different aspects of odor information.