Glomeruli as Functional Units for Olfactory Coding

肾小球作为嗅觉编码的功能单位

• 批准号: 7988568
• 负责人: JOHN G HILDEBRAND
• 金额: $ 27.26万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988568
• 关键词: Address; Affect; Animals; Anosmia; Area; Behavior; Behavioral; Binding; Biological Assay; Biological Models; Biological Neural Networks; Bite; Brain; Characteristics; Chemicals; Chest; Code; Confocal Microscopy; Culicidae; Disease; Exhibits; Food; Foundations; Ganglia; Grant; Health; Homo; Human; Image; Individual; Insect Control; Insecta; Intervention; Label; Lateral; Link; Lobe; Manduca sexta; Measures; Mediating; Monitor; Motor; Neurons; Odors; Olfaction Disorders; Olfactory Pathways; Output; Partner in relationship; Pattern; Pharmaceutical Preparations; Phase; Pheromone; Picrotoxin; Play; Process; Progress Reports; Property; Public Health; Receptor Cell; Research; Role; Science; Sensory; Sensory Process; Series; Sex Attractants; Signal Transduction; Smell Perception; Social Welfare; Source; Specificity; Staining method; Stains; Statistical Methods; Stimulus; Synapses; System; Techniques; Testing; Time; Variant; Work; base; behavior test; detector; experience; extracellular; fly; gamma-Aminobutyric Acid; human disease; hyposmia; insight; male; millisecond; neural circuit; neuromechanism; neurophysiology; olfactory stimulus; postsynaptic; presynaptic; receptor; relating to nervous system; research study; response; sensory stimulus; time interval; vector

DESCRIPTION (provided by applicant): The primary olfactory centers in the brains of humans and most other animals are characterized by an array of synaptic modules called glomeruli, which are organized chemotopically such that chemical information about odor is represented spatially among glomeruli. How sensory information about odor stimuli - and especially mixtures of odor compounds at behaviorally relevant blend proportions - is encoded in neural activity, however, within and among glomeruli before being relayed to higher-order brain areas, is still not well understood. Moreover, studies of the processing of those glomerular outputs downstream in the brain are just beginning. This project builds on a firm foundation of experience with an experimentally favorable model system, the olfactory system of Manduca sexta, which is comparable to its mammalian counterpart in organization and function and is advantageous for neurophysiological testing of hypotheses about neural processing of odor information among glomeruli and thereafter downstream in higher-order brain centers. This model system offers the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and brain neurons, and chemically identified, behaviorally relevant odors. It also provides an excellent opportunity to explore neural relationships within and among identified glomeruli and in higher-order brain centers that receive and further process glomerular outputs, in order to analyze how sensory information about odor compounds and natural, behaviorally relevant mixtures is processed. By means of intracellular recording and staining, extracellular multichannel recording, confocal microscopy, chemical analysis of odor mixtures, behavioral studies and pharmacological interventions, we will investigate identified glomeruli of known odor specificity to test the hypotheses that: (1) synchronous activity (i.e. coincident firing) among the output neurons of glomeruli is an important mechanism for encoding behaviorally significant odor mixtures; (2) such synchronous activity depends on stimulation with mixtures of appropriate chemical composition, concentrations, and blend-proportions of odor components; and (3) the resulting synchronous activity of neurons projecting from glomeruli to higher-order centers is detected by target neurons and is important for their activation and for selective behavioral responses to "meaningful" odor mixtures. The proposed research promises to provide new information about the functional roles of and mechanisms underlying coherent activity of neurons in the olfactory pathway and thus to advance our understanding of olfactory modulation of behavior. Moreover, understanding of neural-network mechanisms underlying the central coding of odor information, gained from this work, should yield insights into the functional changes that accompany disorders of olfaction such as parosmias, hyposmia, and anosmia and at the same time aid efforts to control insects, particularly vectors of devastating diseases that profoundly impact human health and welfare. PUBLIC HEALTH RELEVANCE This research on neural processing of olfactory information in the brain of an experimentally favorable insect model system promises to contribute to our understanding of how neural circuits encode features of sensory stimuli that are essential for appropriate modulation of behavior. Moreover, this line of work further benefits human public health because of the importance of insects as vectors of devastating human diseases (which is based on behaviors all of which depend on olfaction) and the fact that our findings will directly inform research on olfactory-guided behaviors of mosquitoes, kissing bugs, biting flies, and other insects of health importance. This research thus will contribute at once to: understanding of the neural mechanisms underlying odor- information coding in order to gain insights into the functional changes that accompany disorders of olfaction such as parosmias, hyposmia, and anosmia; efforts to control harmful insects that impact human health and welfare; and advances in brain science in general.

描述(申请人提供)：人类和大多数其他动物大脑中的初级嗅觉中心的特征是一系列被称为肾小球的突触模块，这些模块通过化学方法组织起来，使得关于气味的化学信息在肾小球中呈现出来。然而，关于气味刺激的感觉信息--特别是与行为相关的混合比例的气味化合物混合物--是如何在神经活动中编码的，在传递到更高级别的大脑区域之前，在肾小球内和肾小球之间是如何编码的，目前仍不清楚。此外，对这些肾小球输出信号在大脑下游的处理研究才刚刚开始。这个项目建立在一个实验上有利的模型系统Manduca sexta的嗅觉系统的坚实经验基础上，该系统在组织和功能上与其哺乳动物的对应系统相当，并且有利于对关于气味信息在肾小球之间的神经处理的假说进行神经生理学测试，然后在更高阶脑中心的下游。该模型系统具有解剖结构简单、肾小球可识别、受体细胞和脑神经元容易接近以及化学可识别的、行为相关的气味等优点。它还提供了一个极好的机会来探索已识别的肾小球内部和之间的神经关系，以及在接收和进一步处理肾小球输出的高级大脑中心，以便分析关于气味化合物和与行为相关的天然混合物的感觉信息是如何被处理的。通过细胞内记录和染色、细胞外多道记录、共聚焦显微镜、气味混合物的化学分析、行为学研究和药物干预，我们将研究已知气味特异性的肾小球，以检验以下假设：(1)肾小球输出神经元之间的同步活动(即一致放电)是编码行为显著气味混合物的重要机制；(2)这种同步活动依赖于适当的化学成分、浓度和混合比例的气味成分混合物的刺激；(3)从肾小球投射到高阶中枢的神经元由此产生的同步活动被目标神经元检测到，这对它们的激活和对“有意义的”气味混合物的选择性行为反应是重要的。这项研究有望为嗅觉通路中神经元协调活动的功能作用和机制提供新的信息，从而促进我们对嗅觉行为调节的理解。此外，从这项工作中获得的对气味信息中央编码的神经网络机制的理解，应该有助于深入了解伴随着嗅觉障碍(如嗅觉异常、嗅觉减退和嗅觉缺失)的功能变化，同时有助于控制昆虫的努力，特别是深刻影响人类健康和福利的毁灭性疾病的媒介。与公众健康相关这项关于在实验上有利的昆虫模型系统中大脑中嗅觉信息的神经处理的研究有望帮助我们理解神经电路如何编码感觉刺激的特征，这些特征对于适当地调节行为是必不可少的。此外，这项工作进一步有益于人类公共健康，因为昆虫作为毁灭性人类疾病的媒介的重要性(这基于所有依赖嗅觉的行为)，以及我们的发现将直接为蚊子、接吻昆虫、叮咬苍蝇和其他对健康重要的昆虫的嗅觉引导行为的研究提供信息。因此，这项研究将立即有助于：了解气味信息编码背后的神经机制，以洞察伴随嗅觉障碍(如嗅觉异常、嗅觉缺失和嗅觉缺失)的功能变化；努力控制影响人类健康和福利的有害昆虫；以及总体上脑科学的进步。