Connectomic analysis of the Drosophila lateral neuron clock cells reveals the synaptic basis of functional pacemaker classes.
Connectomic analysis of the Drosophila lateral neuron clock cells reveals the synaptic basis of functional pacemaker classes.
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DOI：
10.7554/elife.79139
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发表时间：
2022-06-29
期刊：
影响因子：
7.7
通讯作者：
Fernandez, Maria de la Paz
中科院分区：
文献类型：
--
作者：
Shafer, Orie T.;Gutierrez, Gabrielle J.;Li, Kimberly;Mildenhall, Amber;Spira, Daphna;Marty, Jonathan;Lazar, Aurel A.;Fernandez, Maria de la Paz
生物钟协调生理和行为的日常变化，以确保一天中的内部时间顺序和最佳时间。在动物中，中枢大脑时钟协调整个身体的昼夜节律，其特征在于依赖于组成神经元之间的突触连接的显著鲁棒性。果蝇的时钟神经元网络与哺乳动物大脑中的时钟网络共享网络基序，但由更少的神经元组成，为理解昼夜节律计时的网络特性提供了一个强大的模型。在这里，我们报告了一个时钟网络内的突触连接的评估，重点是关键的侧神经元（LN）的Janelia hemibrain数据集内的时钟神经元类。我们的研究结果表明，以前确定的解剖和功能的LNs亚类代表不同的连接类型。此外，我们确定了少数非时钟细胞亚型代表高度突触耦合节点内的时钟神经元网络。这表明缺乏分子计时的神经元可能在昼夜节律计时网络中发挥着不可或缺的作用。据我们所知，这是第一个全面的昼夜神经元网络的连接组学分析。地球上的大多数生物体都拥有内部的计时系统，确保身体过程，如睡眠，觉醒或消化在正确的时间发生。这些精确的日常节奏由大脑中的主时钟控制。在那里，成千上万的神经元-其中一些携带内部“分子钟”-通过称为突触的结构相互连接。由此产生的网络究竟是如何组织起来支持昼夜节律计时的，目前还不清楚。为了探索这个问题，Shafer，Gutierrez等人专注于果蝇，因为最近的努力已经系统地绘制了这种模式生物大脑中的每个神经元和突触连接。分析来自Janelia的半脑连接体项目的可用数据显示，具有最重要计时作用的神经元实际上在网络中形成最少的突触。此外，没有内部分子钟的神经元在那些有内部分子钟的神经元之间介导了强大的突触连接，这表明“无时钟”细胞仍然在昼夜节律计时中发挥着不可或缺的作用。通过这项研究，Shafer，Gutierrez等人对主生物钟的组织提供了意想不到的见解。更好地理解支撑昼夜节律的网络将有助于理解肥胖、抑郁症和阿尔茨海默病是如何以及为什么这些被破坏的。
The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here, we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes within the Janelia hemibrain dataset. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of non-clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network. Most organisms on Earth possess an internal timekeeping system which ensures that bodily processes such as sleep, wakefulness or digestion take place at the right time. These precise daily rhythms are kept in check by a master clock in the brain. There, thousands of neurons – some of which carrying an internal ‘molecular clock’ – connect to each other through structures known as synapses. Exactly how the resulting network is organised to support circadian timekeeping remains unclear. To explore this question, Shafer, Gutierrez et al. focused on fruit flies, as recent efforts have systematically mapped every neuron and synaptic connection in the brain of this model organism. Analysing available data from the hemibrain connectome project at Janelia revealed that that the neurons with the most important timekeeping roles were in fact forming the fewest synapses within the network. In addition, neurons without internal molecular clocks mediated strong synaptic connections between those that did, suggesting that ‘clockless’ cells still play an integral role in circadian timekeeping. With this research, Shafer, Gutierrez et al. provide unexpected insights into the organisation of the master body clock. Better understanding the networks that underpin circadian rhythms will help to grasp how and why these are disrupted in obesity, depression and Alzheimer’s disease.