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Functional connectomics of a simple brain centre for discrimination and memory

简单大脑中辨别和记忆中心的功能连接组学

基本信息

批准号：
BB/N007948/1
负责人：
Cahir O'Kane
金额：
$ 58.79万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN007948%2F1
关键词：
Functional connectomics simple brain centre

项目摘要

Complex behaviours in animals, including humans, are made possible by the ability of brains to distinguish among an enormous range of sensory cues, and to selectively form and recall memories associated with specific cues. Brains have evolved ways to recognise and remember enormous numbers of sensory cues. It is estimated that humans can distinguish a trillion odors; we can remember very many faces or inanimate objects; and the 2014 Nobel Prize in Physiology and Medicine recognised O'Keefe, Moser and Moser for showing how mammalian brains encode sensory information for specific places. We want to understand the principles of the brain circuitry that recognises and discriminates such a range of cues, and that underlies behaviours that depend on this. Animals as diverse as humans and fruitflies have found common solutions to this challenge - distinct sensory cues, like faces, sounds or smells, cause sparse activity in few scattered neurons in higher brain; and different cues are distinguished by activating different scattered neurons. Since humans have millions of times more neurons than flies, they can distinguish and remember enormously more sensory objects- but the principle of sparse coding is shared between them.How are representations of sensory objects formed and regulated, to maximise the ability of the brain to discriminate among them, and tune representations to the needs of the animal? They must be regulated optimally: if too few neurons respond to a given sensory stimulus, the brain may not take notice of it; but too many, and the neurons that respond to different sensory cues will overlap too much, and the different cues will not be distinguished. Also, many routine sensory cues simply do not have to be remembered - the impact of a sensory experience depends on circumstances like wakefulness, where our attention is directed, or how aroused we are. To answer this question, we need to know the exact organisation of the underlying circuitry: all the neurons involved, the contacts they make, the stimuli they respond to, and their effects on each other. This is easiest in a brain that has few neurons, but still high sensory discrimination, used to form and retrieve memories. Therefore, we will describe the complete circuitry for sensory discrimination in the fruitfly larva (maggot); the main brain structure for this, the mushroom body (MB), has only hundreds of neurons in fruitfly larvae, compared to many billions in humans. A comprehensive map of the neurons and their connections will tell us which other brain regions, or sensory organs, provide information to the mushroom body, or use information provided from it. We, and other scientists who access it, can then formulate and test theories for how the circuitry encodes and regulates specific sensory representations. This will be the first such brain map for any animal.We will do this by tracing each neuron individually through many consecutive thin sections of a larval brain. We will analyse sections at very high magnification, to reveal each neuron's contacts with other neurons. We will then try to identify genetic fly stocks that can target expression of other genes to those neurons, allowing them to be labelled fluorescently, used to monitor neuronal activity, and activated or blocked specifically in living preps. We will prioritise neurons whose anatomy suggests belonging to the circuits that regulate the whole of the MB input region. Finally we will test specific models of how regulation of the MB affects its ability to process sensory information: we will block or activate specific neurons using genetic means, and test the effects of this on activity of other identified neurons, or on the abilities of behaving larvae to discriminate odors.Our work will generate a comprehensive resource for the wider scientific community, to make predictions and assess them experimentally. We expect predictions also to be applicable to more complex brains.

包括人类在内的动物的复杂行为，是由于大脑能够区分大量的感官线索，并有选择地形成和回忆与特定线索相关的记忆。大脑已经进化出识别和记忆大量感官线索的方法。据估计，人类可以区分一万亿种气味;我们可以记住很多面孔或无生命的物体; 2014年诺贝尔生理学和医学奖授予奥基夫，莫泽和莫泽，因为他们展示了哺乳动物大脑如何为特定的地方编码感官信息。我们想了解大脑回路的原理，它能识别和区分这样一系列的线索，并构成依赖于这些线索的行为的基础。像人类和果蝇这样的动物已经找到了应对这一挑战的共同解决方案--不同的感觉线索，如面部、声音或气味，会在高级大脑中的少数分散神经元中引起稀疏活动;不同的线索通过激活不同的分散神经元来区分。由于人类的神经元数量是苍蝇的数百万倍，因此人类可以区分和记忆更多的感官对象--但它们之间共享稀疏编码的原理。感官对象的表征是如何形成和调节的，以最大限度地提高大脑区分它们的能力，并根据动物的需要调整表征？它们必须得到最佳的调节：如果对给定的感觉刺激做出反应的神经元太少，大脑可能不会注意到它;但如果太多，对不同感觉线索做出反应的神经元就会重叠太多，不同的线索将无法区分。此外，许多常规的感官线索根本不需要记住--感官体验的影响取决于诸如清醒的情况，我们的注意力被引导到哪里，或者我们被唤醒的程度。为了回答这个问题，我们需要知道底层电路的确切组织：所有参与的神经元，它们进行的接触，它们对刺激的反应以及它们对彼此的影响。这在神经元很少但仍具有高度感官辨别力的大脑中是最容易的，用于形成和检索记忆。因此，我们将描述果蝇幼虫（蛆）中感觉辨别的完整回路;主要的大脑结构，蘑菇体（MB），在果蝇幼虫中只有数百个神经元，而人类则有数十亿个。神经元及其连接的全面地图将告诉我们，哪些其他大脑区域或感觉器官向蘑菇体提供信息，或使用蘑菇体提供的信息，然后我们和其他访问它的科学家就可以制定和测试关于电路如何编码和调节特定感觉表征的理论。这将是任何动物的第一张此类大脑地图。我们将通过在幼虫大脑的许多连续薄切片中单独追踪每个神经元来做到这一点。我们将在非常高的放大倍数下分析切片，以揭示每个神经元与其他神经元的联系。然后，我们将尝试识别能够将其他基因的表达靶向这些神经元的遗传蝇群，使它们能够被荧光标记，用于监测神经元活动，并在活体准备中特异性激活或阻断。我们将优先考虑那些解剖结构表明属于调节整个MB输入区域的电路的神经元。最后，我们将测试特定的模型如何调节MB影响其处理感官信息的能力：我们将使用遗传手段阻断或激活特定的神经元，并测试这对其他已识别神经元活动的影响，或对行为幼虫辨别气味的能力。我们的工作将为更广泛的科学界提供全面的资源，以进行预测和实验评估。我们希望预测也适用于更复杂的大脑。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

DOI：
10.1101/lm.052159.120
发表时间：
2021-03
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
0
作者：
Wong JYH;Wan BA;Bland T;Montagnese M;McLachlan AD;O'Kane CJ;Zhang SW;Masuda-Nakagawa LM
通讯作者：
Masuda-Nakagawa LM

Mushroom body output neurons MBON-a1/a2 define an odor intensity channel that regulates behavioral odor discrimination learning in larval Drosophila.