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

描述（由申请人提供）：并行处理是不同感觉系统的共同原理。大脑倾向于将感觉刺激的不同方面编码到单独的投射路径中，以执行针对专用特征优化的独特处理。虽然在其他感觉模式中，平行通路已经得到了很好的研究，但嗅觉信号如何通过类似的平行处理回路传递到高阶中枢仍然不清楚。在这项资助中，我建议通过关注嗅球中两种主要类型的投射神经元（僧帽细胞和簇状细胞）来探索这个问题。虽然早期的神经元形态学分析表明，它们可能代表两个独立的气味处理途径，但它们的功能差异尚未得到很好的表征。这主要是由于这样一个事实，即在不知道感兴趣的神经元是否从共同或不同的肾小球接收嗅觉输入的情况下，很难比较气味反应特性。此外，目前还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，它结合了葡聚糖染料局部电穿孔和体内双光子钙成像，以实现同时跟踪神经回路和成像的细胞功能。一个系统的比较分析将进行共享一个共同的肾小球输入的二尖瓣和簇状细胞的气味反应配置文件，在寻找他们是如何不同地参与编码和处理不同的气味功能的见解。根据我目前的初步数据，我将进一步测试的假设，二尖瓣和簇状细胞显示不同的偏好，他们的轴突终止领域。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，二尖瓣和簇状细胞确实构成了两个平行的处理不同气味信息的处理途径。 公共卫生相关性：所有的感觉系统基本上都在我们的大脑和外部环境之间提供了一个平行的界面。在视觉和听觉系统中，感觉输入的并行处理的神经机制已经得到了很好的研究。然而，对于嗅觉，这对我们的日常生活质量至关重要，它仍然是迄今为止知之甚少，如何在这个系统中实现这种并行信号处理机制，特别是在神经元电路水平。我在这里提出了一系列的实验来验证这一假设，即两种主要类型的主要神经元在嗅球，僧帽细胞和簇状细胞，显示完全不同的气味反应的配置文件和中央轴突投射模式。这种差异使这些神经元能够在两个平行的气味处理途径中发挥骨干作用，这两个途径涉及处理气味信息的不同方面。

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.