Processing of temporally dynamic olfactory inputs

描述(申请人提供)：这项研究的目标是了解气味信息是如何由神经系统编码的。最初，气味与嗅觉感受器神经元结合，嗅觉感受器神经元投射到嗅球中的肾小球，这是嗅觉信息处理的第一阶段。在这里，数千个感受器神经元的活动模式被转换成肾小球激活的空间组织图。这些肾小球受体输入的映射是时间动态的，它们的大部分时间动态是围绕呼吸周期组织的。这个项目的研究将探讨如何将肾小球的感受器神经元的动力学转化为从嗅球投射到皮质(二尖瓣/簇状细胞)的输出神经元的放电模式。投射神经元本身也显示出围绕呼吸周期组织的复杂放电模式--事实上，有人假设它们之间的放电相对时间对嗅觉编码很重要--但这些复杂动力学的来源尚未确定。这个项目将测试这样一种想法，即在自然气味采样(即嗅觉)过程中诱发的感觉输入的时间动力学是二尖瓣/簇状细胞反应模式的强烈决定因素。该项目将首次研究气味采样行为如何影响嗅球水平的早期嗅觉编码，以及受体输入到突触后活动模式的转换。这里提出的实验将使用光学成像方法直接可视化气味诱发的肾小球映射，以及电生理技术来记录二尖瓣/簇状细胞的活动，重点是对气味的自然采样引起的反应。此外，一个简单的二尖瓣细胞生物物理计算模型将被实施和测试，以确定其对自然肾小球输入的反应。除了第一次测试关于采样行为在形成气味代码中的作用的几个长期假设之外，这项工作对于理解嗅觉信息在清醒的行为动物中是如何编码和处理的将是重要的。 与公共健康相关：了解嗅觉系统功能的基本原理可以增加对神经系统如何处理感官信息的理解，包括视觉、听觉或与触摸相关的输入；这些见解对于开发人类(例如，视障人士)的人工感官可能很重要。对哺乳动物神经系统功能的更多了解也有可能导致改善神经系统疾病的诊断和治疗。

DESCRIPTION (provided by applicant): The goal of this research is to understand how odor information is encoded by the nervous system. Initially, odorants bind to olfactory receptor neurons, which project to glomeruli in the olfactory bulb, the first stage of olfactory information processing. Here, patterns of activity across thousands of receptor neurons are transformed into spatially organized maps of glomerular activation. These maps of receptor input to glomeruli are temporally dynamic, and much of their temporal dynamics are organized around the respiratory cycle. The research in this project will ask how the dynamics of receptor neuron to a glomerulus are translated into firing patterns in the output neurons that project from the olfactory bulb to the cortex (mitral/tufted cells). The projection neurons themselves exhibit complex firing patterns also organized around the respiratory cycle - in fact, it has been hypothesized that the relative timing of firing among them is important for olfactory coding - but the source of these complex dynamics has not yet been identified. This project will test the idea that the temporal dynamics of sensory input evoked during natural odor sampling (i.e., sniffing) is a strong determinant of mitral/tufted cell response patterns. The project will investigate, for the first time, how odor sampling behavior shapes both early olfactory coding at the level of the olfactory bulb and the transformation of receptor inputs into patterns of postsynaptic activity. The experiments proposed here will use optical imaging methods to directly visualize odor-evoked glomerular maps, as well as electrophysiological techniques to record activity from mitral/tufted cells, focusing on responses evoked by naturalistic sampling of odorants. In addition, a simple biophysical computational model of a mitral cell will be implemented and tested to determine its response to naturalistic glomerular input. In addition to testing, for the first time, several longstanding hypotheses about the role of sampling behavior in shaping odor codes, this work will be important in understanding how olfactory information is encoded and processed in the awake, behaving animal. PUBLIC HEALTH RELEVANCE: Understanding the basic principles of olfactory system function can lead to an increased understanding of how the nervous system processes sensory information, including visual, auditory, or touch-related input; such insights could be important in developing artificial sensory organs for humans (for the visually-impaired, for example). Understanding more about mammalian nervous system function also has the potential to lead to improved diagnosis and treatment of diseases of the nervous system.