CRCNS: Active Sensing and Odor Processing in the Olfactory Bulb

描述(申请人提供)：感觉是一个活跃的过程，涉及动物与其环境的动态相互作用，导致感觉神经元和最终构成感知的中央处理阶段的神经活动的动态模式。这个拟议的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力学、感觉输入到嗅觉系统的时间结构之间的关系，以及这两个因素如何塑造嗅球的处理-哺乳动物嗅觉系统信息处理的第一阶段。时间上的动态活动模式是许多不同水平的嗅觉处理的显著特征，而在慢(100-500毫秒)和快(10-50毫秒)时间尺度上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态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，尚不清楚感觉输入的时间结构如何塑造气味表征和信息处理。此外，在有行为的动物身上，呼吸本身是高度动态的，动物在气味采样(即嗅觉)过程中主动改变个体嗅觉的频率、幅度和形状。到目前为止，很少有研究研究这些采样行为的变化--以及嗅觉驱动的感觉输入--对高阶嗅觉处理的影响。与此同时，最近的研究指出，嗅球肾小球层的电路在通过二尖瓣细胞塑造球输出方面具有重要作用。这些新描述的电路还没有被整合到嗅球功能的生物物理现实的计算模型中。该项目将使用实验和计算相结合的方法来解决两个核心问题： 1.肾小球回路如何将现实的感觉输入模式转换为二尖瓣细胞输出模式？ 2.嗅球改变对二尖瓣细胞群代表气味有什么影响？ 智力价值：该项目是一项联合的实验和计算工作，使用清醒的、表现为啮齿动物的感觉神经元活动的时空模式作为嗅球网络计算模型的输入。该项目还将使用电生理和行为测量来测试模型预测。这种方法是独特和重要的，因为它第一次使用了嗅球功能模型的自然感觉输入，也因为它第一次结合了嗅球小球周围电路的真实模型，其中的许多特征直到最近才被描述。这些实验旨在提供一幅图，展示气味信息在突触处理的第一阶段是如何转化的，以及这种转化是如何被动物自己的采样行为主动塑造的。 更广泛的影响：拟议的工作应该导致对感觉如何被感觉获得行为主动调节的重要见解。这项工作的一个潜在的重要生物医学影响是改进的假肢设备的开发-例如，使用传感器驱动的本体感觉信息来帮助控制运动的假肢。另一个潜在的影响是改进了传感器设备的设计，以便在复杂的环境中检测分析物。将自然主义的感觉信息作为模型电路的输入的一般概念，也可能导致在理解其他形式的感觉处理方面的重要突破。最近在嗅球中描述的肾小球网络的第一个电路模型的产生将是该领域中希望描述嗅觉系统中最初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.