CRCNS: Active Sensing and Odor Processing in the Olfactory Bulb

描述（由申请人提供）：感觉是一种涉及动物与其环境的动态相互作用的主动过程，其导致感觉神经元和最终构成感知基础的中枢处理阶段中的神经活动的动态模式。该项目将研究清醒动物的感觉系统功能，使用嗅觉系统来了解刺激采样的动态之间的关系，嗅觉系统的感觉输入的时间结构，以及这两个因素如何塑造嗅球中的处理-哺乳动物嗅觉系统中信息处理的第一阶段。时间动态活动模式是许多不同水平的嗅觉处理的突出特征，并且在慢（100 - 500毫秒）和快（10 - 50毫秒）时间尺度下的动态活动是许多气味编码模型的核心。在所有这些水平上，气味诱发活动的大部分动力学都是围绕呼吸周期构建的，呼吸周期控制着气味进入感觉神经元本身。然而，目前还不清楚的感觉输入的时间结构形状的气味表征和信息处理。此外，在行为动物中，呼吸本身是高度动态的，其中动物在气味采样期间主动地改变个体嗅闻的频率、幅度和形状（即，嗅闻）。到目前为止，很少有研究探讨这些变化的后果，在采样行为-在嗅探驱动的感官输入-高阶嗅觉处理。与此同时，最近的研究指出，在通过二尖瓣细胞形成球输出的嗅球的肾小球层中的电路的重要性。这些新描述的电路还没有被纳入一个生物病理学现实，计算模型的嗅球功能。该项目将使用实验和计算方法的组合来解决两个核心问题： 1.肾小球回路如何将感觉输入的现实模式转化为二尖瓣细胞输出的模式？ 2.嗅球的转化对僧帽细胞群表达气味的影响是什么？ 智力优势：该项目是一个联合实验和计算的努力，它使用从清醒的，行为啮齿动物记录的感觉神经元活动的时空模式作为嗅球网络的计算模型的输入。该项目还将使用电生理和行为测量来测试模型预测。这种方法是独特的和重要的，因为它使用-第一次-自然的感觉输入的嗅球功能的模型，也因为它纳入-第一次-一个现实的模型周围的嗅球肾小球的电路，其中许多功能只是最近才被描述。这些实验的目的是提供一个图片的气味信息是如何转换在突触处理的第一阶段，以及这种转换是如何积极塑造动物自己的采样行为。 更广泛的影响：拟议的工作应该导致重要的见解，感觉如何可以积极调制的感觉获得行为。这项工作的一个潜在的重要生物医学影响是改进假肢设备的开发-例如，使用传感器驱动的本体感受信息来帮助控制运动的假肢。另一个潜在的影响是用于在复杂环境中检测分析物的传感器设备的改进设计。使用自然感觉信息作为模型电路的输入的一般概念也可能导致理解其他形式的感觉处理的重要突破。最近描述的嗅球中的肾小球网络的第一个电路模型的生成将是该领域中希望表征嗅觉系统中前几个突触的计算的其他人的重要共享资源。

DESCRIPTION (provided by applicant): Sensation is an active process involving dynamic interactions of the animal with its environment, which leads to dynamic patterns of neural activity in sensory neurons and in the central processing stages that ultimately underlie perception. The proposed project will investigate sensory system function in the awake animal, using the olfactory system to understand the relationship between the dynamics of stimulus sampling, the temporal structure of sensory inputs to the olfactory system, and how these two factors shape processing in the olfactory bulb - the first stage of information processing in the mammalian olfactory system. Temporally dynamic activity patterns are a prominent feature of many different levels of olfactory processing, and dynamic activity at both slow (100 - 500 msec) and fast (10 - 50 ms) timescales is central to many models of odor coding. Much of the dynamics of odorant-evoked activity - at all of these levels - is structured around the respiratory cycle, which controls the access of odorant to the sensory neurons themselves. However, it remains unclear how the temporal structure of sensory input shapes odor representations and information processing. In addition, in the behaving animal respiration itself is highly dynamic, with animals actively changing the frequency, amplitude, and shape of individual sniffs during odor sampling (i.e., sniffing). Very few studies to date have examined the consequences of these changes in sampling behavior - and in the sniff-driven sensory input - for higher-order olfactory processing. At the same time, recent studies have pointed to the importance of circuitry in the glomerular layer of the olfactory bulb in shaping bulb output via mitral cells. These newly-described circuits have yet to be incorporated into a biophysically-realistic, computational model of olfactory bulb function. This project will use a combination of experimental and computational approaches to address two central questions: 1. How does the glomerular circuitry transform realistic patterns of sensory input into patterns of mitral cell output? 2. What are the consequences of the olfactory bulb transformation for the representation of odorants by mitral cell populations? Intellectual Merit: The project is a joint experimental and computational effort which uses spatiotemporal patterns of sensory neuron activity recorded from awake, behaving rodents as inputs to computational models of the olfactory bulb network. The project will also use electrophysiological and behavioral measures to test model predictions. This approach is unique and significant in that it uses - for the first time - natural sensory inputs to a model of olfactory bulb function, and also because it incorporates - for the first time - a realistic model of the circuitry around the olfactory bulb glomerulus, many features of which have only recently been described. The experiments are designed to provide a picture of how odor information is transformed at the first stage of synaptic processing and how this transformation is actively shaped by the animal's own sampling behavior. Broader Impacts: The proposed work should lead to important insights into how sensation can be actively modulated by sensory acquisition behavior. A potentially important biomedical impact of this work is the development of improved prosthetic devices - for example, artificial limbs which use sensor-driven proprioceptive information to help control movement. Another potential impact is the improved design of sensor devices for detecting analytes in a complex environment. The general concept of using naturalistic sensory information as inputs to model circuits is an idea that could also lead to important breakthroughs in understanding sensory processing in other modalities. Generation of the first circuit model of the recently-described glomerular network in the olfactory bulb will be an important shared resource for others in the field who wish to characterize computations at the first few synapses in the olfactory system.