Glomeruli as Functional Units for Olfactory Coding

描述（由申请人提供）：人类和大多数其他动物脑中的初级嗅觉中心的特征在于称为肾小球的突触模块阵列，其以化学拓扑方式组织，使得关于气味的化学信息在肾小球中空间地表示。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的混合物-在神经活动中如何编码，在被传递到高阶脑区之前在肾小球内和肾小球之间，仍然没有很好地理解。此外，对这些肾小球输出在大脑下游的处理的研究才刚刚开始。该项目建立在坚实的基础上的经验与实验有利的模型系统，嗅觉系统的天蛾，这是其哺乳动物对应的组织和功能，是有利的神经生理学测试的假设有关神经处理的气味信息之间的肾小球和下游的高阶脑中心。该模型系统提供了解剖简单，可识别的肾小球，可访问的受体细胞和脑神经元，和化学识别，行为相关的气味的优点。它还提供了一个很好的机会，探索神经内和之间的关系，确定肾小球和高阶脑中心，接收和进一步处理肾小球输出，以分析如何感觉信息的气味化合物和自然的，行为相关的混合物处理。通过细胞内记录和染色、细胞外多通道记录、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，以验证以下假设：（1）同步活动肾小球输出神经元之间的同步放电（即同步放电）是编码行为上重要的气味混合物的重要机制;（2）这种同步活动取决于用气味成分的适当化学组成、浓度和混合比例的混合物进行的刺激;和（3）由靶神经元检测到从肾小球投射到高级中心的神经元的所得同步活动，并且对于它们的激活和对“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相干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调节行为的理解。此外，从这项工作中获得的气味信息的中央编码的神经网络机制的理解，应该产生的功能变化，伴随嗅觉障碍，如嗅觉减退，嗅觉减退和嗅觉丧失的见解，并在同一时间的援助努力，以控制昆虫，特别是毁灭性的疾病，深刻影响人类健康和福利的载体。公共卫生相关性这项关于实验上有利的昆虫模型系统的大脑中嗅觉信息的神经处理的研究有望有助于我们理解神经回路如何编码对适当的行为调节至关重要的感觉刺激的特征。此外，由于昆虫作为毁灭性人类疾病的载体的重要性（这是基于所有依赖嗅觉的行为），以及我们的研究结果将直接为蚊子的嗅觉引导行为的研究提供信息，接吻虫，叮咬苍蝇和其他对健康有重要意义的昆虫。因此，这项研究将有助于：了解气味信息编码的神经机制，以便深入了解伴随嗅觉障碍（如嗅觉异常、嗅觉减退和嗅觉丧失）的功能变化;努力控制影响人类健康和福利的有害昆虫;以及一般脑科学的进步。

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.