Dynamics of Glomerular Coding in the Olfactory Bulb

描述（由申请人提供）：本研究的目的是了解神经系统如何编码有关气味的信息。嗅觉在刺激检测、神经编码和复杂刺激的识别方面对神经系统提出了独特的问题；了解大脑是如何解决这些问题的，可能会让我们对大脑如何处理信息有更全面的了解。气味的初始编码由嗅觉受体神经元的活动模式组成，这些活动模式投射到嗅球的肾小球，嗅球是嗅觉信息突触处理的第一阶段。在这里，数千个受体神经元的活动模式被转化为肾小球活动的空间组织图-这些肾小球模式对于给定的气味和气味浓度是独特的。这个正在进行的项目的研究使用光学成像方法来可视化这些模式，并研究它们如何代表嗅觉刺激。先前的工作建立在观察肾小球受体输入的空间图是时间动态的基础上，并询问这些动态如何参与气味编码并塑造嗅觉加工的初始阶段。一个关键的发现是，气味地图的大部分时间动态都是围绕呼吸周期组织的，呼吸周期在清醒的动物中受到严重调节，是嗅觉行为的组成部分。本文提出的实验将首次研究气味取样行为（即“嗅探”）如何在嗅球水平上形成早期嗅觉编码，以及受体输入如何转化为突触后活动模式。实验将在动物清醒并积极执行气味引导任务时对嗅球肾小球的受体输入进行成像，并将这些模式与动物的嗅闻行为联系起来。不同的嗅探模式也将在麻醉动物中播放，以便分别评估取样行为的影响和行为状态依赖性受体输入调节的影响。实验还将探讨嗅探如何影响嗅球对气味表征的转换，利用不同嗅探模式下取样的气味激活过程中单个嗅球投射神经元的电生理记录。除了首次测试关于采样行为在形成气味编码中的作用的几个长期存在的假设外，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也很重要。这项工作有可能导致嗅觉缺陷的新治疗方法或改善鼻功能受损个体的气味或味道感知的治疗方法。公共卫生相关性：嗅觉在刺激检测、神经编码和复杂刺激识别方面对神经系统提出了独特的问题；了解大脑是如何解决这些问题的，可能会让我们对大脑如何处理信息有更全面的了解。这个项目特别关注呼吸行为在决定大脑如何表现和处理嗅觉信息方面的重要性。了解这种关系可能会导致嗅觉缺陷的新治疗方法或改善鼻功能受损个体的气味或味道感知的治疗方法。

Description (provided by applicant): The goal of this research is to understand how the nervous system encodes information about odors. The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli; understanding how the brain solves these problems will likely lead to new general insights into how the brain processes information. The initial code for odors consists of patterns of activity across olfactory receptor neurons, which project to glomeruli in the olfactory bulb, the first stage of synaptic processing of olfactory information. Here, patterns of activity across thousands of receptor neurons are transformed into spatially organized maps of glomerular activation - these glomerular patterns are unique for a given odor and odor concentration. The research in this continuing project uses optical imaging methods to visualize these patterns and to investigate how they represent olfactory stimuli. Previous work built on the observation that spatial maps of receptor input to glomeruli are temporally dynamic, and asked how these dynamics participate in odor coding and shape the initial stages of olfactory processing. A key finding was that much of the temporal dynamics of odor maps are organized around the respiratory cycle, which is heavily modulated in the awake, behaving animal and is integral to the act of smelling. The experiments proposed here will investigate, for the first time, how odor sampling behavior (i.e. - `sniffing') shapes early olfactory coding at the level of the olfactory bulb and the transformation of receptor inputs into patterns of postsynaptic activity. The experiments will image receptor input to olfactory bulb glomeruli while an animal is awake and actively performing odor-guided tasks, and relate these patterns to the animal's sniffing behavior. Different patterns of sniffing will also be played back in the anesthetized animal in order to separately evaluate effects of sampling behavior and effects of behavioral state-dependent modulation of receptor inputs. The experiments will also ask how sniffing shapes the transformation of odor representations by the olfactory bulb, using electrophysiological recordings from individual olfactory bulb projection neurons during activation by odorants sampled with different sniffing patterns. 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. This work has the potential to lead to new treatments for olfactory deficits or therapeutic approaches to improving odor or flavor perception in individuals with impaired nasal function. PUBLIC HEALTH RELEVANCE: The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli; understanding how the brain solves these problems will likely lead to new general insights into how the brain processes information. This project in particular focuses on the importance of respiratory behavior in determining how the brain represents and processes olfactory information. Understanding this relationship could lead to new treatments for olfactory deficits or therapeutic approaches to improving odor or flavor perception in individuals with impaired nasal function.