The effect of periodic input on measures of olfactory processing and perception

描述（由申请人提供）：我们对周期性输入对中枢嗅觉表征的功能意义的理解存在根本性的差距。我们的长期目标是了解气味编码的神经基础，以及这个过程如何反过来影响感知和行为。本应用程序的目的是表征周期性输入的动态如何影响嗅觉感知，并确定负责优化嗅觉反应的生理机制。我们的中心假设是，嗅觉系统已经进化到对周期性刺激而不是连续刺激做出最佳反应，这种能力是由局部触角叶加工和离心输入介导的，而离心输入与翅膀运动的产生有关。这项研究的基本原理是，一旦我们理解了周期性输入是如何增强初级嗅觉功能的，我们就能更好地描述中枢表征及其与感知的关系。此外，这些数据将为基本启发式提供新的见解，通过这些启发式，可以将更好的人工嗅觉传感器用于人类健康和安全的诊断用途。因此，拟议的研究与NIH的使命有关，即获取“关于生命系统的性质和行为以及这些知识的应用的基本知识”，特别是关于人类疾病的诊断和预防。在强有力的初步数据的指导下，这一假设将在两个具体目标上进行验证：1)确定周期性刺激的特征，优化气味处理和敏锐性的神经行为基础；2)研究增强脉冲感觉输入的神经和行为反应的细胞机制。Aim 1的工作假设是由翅膀拍打周期引起的天线周围的气流动力学影响神经表征，从而增强了心理物理测量的嗅觉灵敏度。Aim 2的工作假设是，触角叶局部突触活动的相互作用与来自其他大脑区域的输入一起工作，以积极地门输入。该研究结果具有创新性，因为它们阐明了周期性输入如何影响嗅觉刺激的输入和初级加工，以及由此产生的神经表征变化如何影响感官知觉。此外，我们建立了介导离散脉冲跟踪行为的神经生理基础的机制，并建立了这些机制的破坏如何反过来影响嗅觉敏锐度。这项研究意义重大，因为中枢嗅觉处理，以及人工复制这一过程的尝试，都依赖于感官阵列与环境的初始相互作用。这项工作的结果将为以下方面提供新的见解：1)周期输入的普遍性；2)输入对气味加工的时间约束；3)是否需要多个嗅觉样本并进行整合；4)偏离正常嗅觉取样的后果；5)输入信号的门控机制；6)正在努力设计更好的基于嗅觉的传感器。公共卫生相关性：拟议的研究是一个重要但尚未充分研究的嗅觉领域，有可能阐明气味检测和辨别的最佳刺激参数以及这种优化背后的生理机制。拟议的研究与公共卫生直接相关，因为它们将建立生物系统优化气味信号处理的参数；这反过来将有助于人工探测器的设计。这种检测器用于诊断人类疾病和检测环境中的有害化学痕迹，作为疾病预防措施。

Description (provided by applicant): There is a fundamental gap in our understanding of the functional significance that periodic input has on cen- tral olfactory representations. Our long-term goal is to understand the neural basis of odor encoding and how this process in turn affects perception and behavior. The objective of this application is to characterize how the dynamics of periodic input affect olfactory perception and identify the physiological mechanisms responsible for optimizing olfactory responses. Our central hypothesis is that olfactory systems have evolved to respond optimally to periodic rather than continuous stimulation and that this ability is mediated by local antennal lobe processing and centrifugal input that is related to the generation of wing movement. The rationale underlying the research is that, once we understand how periodic input enhances primary olfactory function, we will be better able to characterize central representations and their relationship to perception. Furthermore, these data will provide new insights into the fundamental heuristics through which better artificial olfactory sensors can be implemented for diagnostic use in human health and safety. The proposed re- search is therefore relevant to that part of NIH's mission that pertains to the acquisition of "fundamental knowledge about the nature and behavior of living systems and the application of that knowledge" particularly with respect to diagnosis and prevention of human diseases. Guided by strong preliminary data, this hypothesis will be tested in two specific aims: 1) Determine the characteristics of periodic stimulation that optimize the neurobehavior basis of odor processing and acuity; and 2) Investigate cellular mechanisms that enhance neural and behavioral responses to pulsed sensory input. The Aim 1 working hypothesis is the dynamics of airflow around the antennae induced by the wing beat cycle affect the neural representations in a way that enhances olfactory acuity as measured psychophysically. The working hypothesis for Aim 2 is that the interaction of local synaptic activity in antennal lobe work in conjunction with input from other brain regions to actively gate input. The results of the proposed research are innovative because they elucidate how input and primary processing of olfactory stimuli are affected by periodic input and how resulting changes in neural representation affect sensory perception. Furthermore we establish the mechanisms that mediate the neurophysiological basis of discrete pulse tracking behavior and establish how disruption of these mechanisms, in turn affects olfactory acuity. The proposed research is significant because central olfactory processing, as well as attempts to replicate this process artificially, are both dependent on the initial interaction of the sensory array with the environment. The results of this work will provide new insights into: 1) the universality of periodic input; 2) the temporal constraints input places on odor processing; 3) whether multiple olfactory samples are necessary and are integrated; 4) the consequences of deviating from normal olfactory sampling; 5) the mechanisms for gating input signals; and 6) ongoing efforts to design better olfactory based sensors. PUBLIC HEALTH RELEVANCE: The proposed studies are an important yet understudied area of olfaction that has the potential of elucidating optimal stimulus parameters for odor detection and discrimination and the physiological mechanisms that underlie this optimization. The proposed research has direct relevance to public health because they will establish parameters by which biological systems optimize odor signal processing; this in turn will aid design of artificial detector designs. Such detectors are used for diagnosis of human disease and detection of hazardous chemical traces in the environment as a disease prevention measure.