Processing of temporally dynamic olfactory inputs

描述（由申请人提供）：本研究的目的是了解气味信息是如何由神经系统编码的。最初，气味与嗅觉受体神经元结合，嗅觉受体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，数千个受体神经元的活动模式被转化为肾小球激活的空间组织图。这些地图的受体输入肾小球是时间动态的，和他们的大部分时间动态组织周围的呼吸周期。该项目的研究将询问受体神经元到肾小球的动力学如何转化为从嗅球投射到皮层的输出神经元（二尖瓣/簇状细胞）的放电模式。投射神经元本身也表现出复杂的放电模式，也是围绕呼吸周期组织的--事实上，人们已经假设它们之间的相对放电时间对嗅觉编码很重要--但这些复杂动力学的来源还没有被确定。该项目将测试的想法，即在自然气味采样过程中诱发的感觉输入的时间动态（即，嗅闻）是二尖瓣/簇状细胞反应模式的强决定因素。该项目将首次研究气味采样行为如何在嗅球水平上塑造早期嗅觉编码以及受体输入转化为突触后活动模式。本文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地图，以及电生理技术记录二尖瓣/簇状细胞的活动，重点是气味的自然采样引起的反应。此外，一个简单的生物物理计算模型的二尖瓣细胞将实施和测试，以确定其响应自然肾小球输入。除了第一次测试几个长期存在的关于采样行为在形成气味代码中的作用的假设外，这项工作对于理解嗅觉信息如何在清醒的行为动物中编码和处理非常重要。 公共卫生相关性：了解嗅觉系统功能的基本原理可以提高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人工感觉器官（例如视觉受损）非常重要。更多地了解哺乳动物神经系统功能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.