Olfactory Coding in the Insect Pheromone Pathway: Models and Experiments

“通过研究简单的系统，我们可以了解复杂的系统。[…“小型系统，尤其是小型嗅觉系统，似乎使用的机制和策略并不是它们所独有的，我们最好先从了解苍蝇这个适度的目标开始。”劳伦特：我们能理解苍蝇的大脑吗？《系统神经科学中的23个问题》，牛津大学出版社，2006年。由于实际和伦理原因，我们对发生在人脑中的计算的理解受到皮层极端复杂性和实验记录神经活动的困难的限制。正如人类基因组计划之前是对更小但完整的基因组进行测序一样，未来神经科学的突破很可能来自对更小但完整的神经系统的研究，比如昆虫的大脑。这些小的神经系统表现出在高等哺乳动物中也存在的一般特性，比如神经同步和网络振荡，在我们将这些知识应用于人类之前，我们更有可能首先了解这些现象在昆虫中的作用。这个项目分析嗅觉，嗅觉，并使用飞蛾嗅觉脑作为模型，因为(i)它相对简单，（ii）它已经被广泛描述，（iii）它很容易获得电生理记录。我们的目的是了解在气味刺激的检测和处理过程中，感官信息是如何编码和处理的，特别强调性信息素的交流。信息素交流构成了研究嗅觉机制的一个非常有利的模型系统，因为(i)它是专门的和定向的（释放雌性，接收雄性），（ii）它只涉及少量已知和可用的配体（性信息素），与特定的膜受体相互作用，（iii）处理信息素信息的大脑神经网络被很好地划分和专门化，（iv）行为反应被很好地表征。飞蛾的嗅觉大脑由三组神经元组成：(a)触角上的嗅觉受体神经元（orn），它们大量地检测和编码信息素信号的质量（分子的性质）、强度（分子的数量）和时间特征；(b)神经元，特别是大脑天线叶（AL）的投射神经元（PNs）数量较少，整合了神经元传递的信息。所有的突触连接，在orn、AL神经元和大脑其他部分的调节神经元之间，都发生在一组约60个肾小球中。特别是，由2-3个增大的两性二态肾小球组成的一个亚群，即大肾小球复合物（MGC），处理信息素信息。(c)大量蘑菇体的凯尼恩细胞处理从PNs接收的信息。这种神经系统具有重要的科学和社会经济意义。虽然嗅觉的研究长期被忽视，但在过去的十五年中，由于对其分子和神经机制的兴趣以及在许多领域的潜在应用，嗅觉的研究有了相当大的扩展。后者包括控制昆虫数量和“人工鼻子”（一个迅速扩大的具有相当经济重要性的领域）。本文提出的研究将探讨生物嗅觉系统优越性能背后的原理，从而为这些领域的新发展提供基础。

'Much can be learned about complex systems by studying simpler ones. [...] Small systems, and particularly small olfactory systems, seem to use mechanisms and strategies that are not unique to them and we may be better off starting with the modest goal of understanding flies first.' G. Laurent 'Shall we even understand the fly brain?' in 23 Problems in Systems Neuroscience, Oxford University Press, 2006. Our understanding of the computations that take place in the human brain is limited by the extreme complexity of the cortex, and by the difficulty of experimentally recording neural activities, for practical and ethical reasons. Just as the Human Genome Project was preceded by the sequencing of smaller but complete genomes, it is likely that future breakthroughs in neuroscience will result from the study of smaller but complete nervous systems, such as the insect brain. These small nervous systems exhibit general properties that are also present in higher mammals, such as neural synchronization and network oscillations, and we are more likely to understand the role of these phenomena in insects first, before we can apply this knowledge to humans. This project analyzes olfaction, the sense of smell, and uses the moth olfactory brain as a model, because (i) it is relatively simple, (ii) it has been widely described and (iii) it is easily accessible to electrophysiological recordings. Our aim is to understand how sensory information is coded and processed during the detection and processing of odour stimuli, with special emphasis on communication by sexual pheromones. Pheromonal communication constitutes an exceptionally favourable model system for studying olfactory mechanisms, because (i) it is specialized and oriented (emitting females, receiving males), (ii) it involves only a small number of known and available ligands (sexual pheromones) which interact with specific membrane receptors, (iii) the cerebral neural network processing pheromonal information is well delimited and specialized, and (iv) the behavioural response is well characterized. The moth olfactory brain is made of three sets of neurons: (a) the olfactory receptor neurons (ORNs) of the antenna, in large numbers, detect and code the quality (nature of molecules), intensity (number of molecules) and temporal characteristics of the pheromonal signal; (b) the neurons, especially the projection neurons (PNs) of the antennal lobe (AL) in the brain, in smaller numbers, integrate the information delivered by ORNs. All synaptic connections, between ORNs, AL neurons and modulatory neurons from other parts of the brain, take place in a set of ca. 60 glomeruli. In particular, a subset of 2-3 enlarged, sexually dimorphic glomeruli, the macroglomerular complex (MGC), processes the pheromonal information. (c) The Kenyon cells of the mushroom bodies (MBs), in large numbers, process the information received from the PNs. This neural system is of significant scientific and socio-economic interest. Although long neglected, the study of olfaction has considerably expanded over the last fifteen years, stimulated by the interest in its molecular and neural mechanisms as well as the potential applications in many areas. Among the latter are the control of insect populations and 'artificial noses' (a rapidly expanding area of considerable economic importance). The research proposed here will investigate the principles underlying the superior performance of biological olfactory systems and thus will provide the basis for novel developments in these fields.