果蝇电子显微镜连接组数据库及相关神经环路功能解析的研究进展

doi:10.12300/j.issn.1674-5817.2025.147

摘要/Abstract

摘要：

近年来，黑腹果蝇（Drosophila melanogaster）的电子显微镜连接组研究取得重大突破，提供了全脑尺度下突触分辨率的神经环路图谱。本文综述果蝇电子显微镜连接组数据库从脑区局部重建到全脑完整绘制的发展历程，重点总结其在解析神经环路研究领域三大核心问题中发挥的作用：在感觉信息编码方面，以视觉系统为例揭示运动检测与颜色处理的机制；在行为决策方面，阐明雌蝇交配与产卵抉择的环路基础；在运动控制方面，解析雄蝇求偶歌曲模式生成的神经机制。这些成果揭示了结构连接与功能特化的关系和信息分级整合与并行-层级控制的机制，在极大程度上深化了对神经环路“结构-功能”关系的理解。文末展望电子显微镜连接组在跨物种比较、全脑动态网络建模及计算-实验融合等方向运用的潜力，这些探索有助于推动神经科学从局部推测转向全脑精准解析的范式革新，为复杂生物连接组研究提供技术模板与理论锚点，搭建基础神经环路与人类神经疾病的研究桥梁，并为类脑智能计算提供生物原型，为探索神经系统的进化规律和工作机制提供重要启示。

关键词: 黑腹果蝇, 电子显微镜, 连接组, 数据库, 神经环路

Abstract:

In recent years, research on the electron microscopy connectome of Drosophila melanogaster has achieved major breakthroughs, providing neural circuit maps with synaptic resolution across the whole brain. This review outlines the development history of Drosophila electron microscopy connectome databases from local brain region reconstruction to comprehensive whole-brain mapping, and highlights their role in addressing three core problems in neural circuit research field: in terms of sensory information encoding, the visual system is used as an example to reveal mechanisms of motion detection and color processing; in terms of behavioral decision-making, the circuit basis underlying female mating and egg-laying choices is elucidated; and in terms of motor control, the neural mechanisms underlying courtship song pattern generation in males are analyzed. These advances reveal the relationship between structural connectivity and functional specialization, as well as mechanisms of hierarchical integration and parallel-hierarchical control of information, greatly deepening our understanding of the "structure-function" relationship in neural circuits. At the end of this article, the potential applications of electron microscope connectomes in areas such as cross-species comparison, whole-brain dynamic network modeling, and computation-experiment integration are discussed. These explorations help promote a paradigm revolution in neuroscience from local speculation to precise whole-brain analysis, provide technical templates and theoretical anchor points for connectome research in complex organisms, build a research bridge between basic neural circuits and human neurological diseases, offer biological prototypes for brain-inspired intelligent computing, and provide important insights for exploring the evolutionary laws and working mechanisms of the nervous system.

Key words: Drosophila melanogaster, Electron microscopy, Connectome, Database, Neural circuits

中图分类号:

Q95-33

邓贤铭,汪菲. 果蝇电子显微镜连接组数据库及相关神经环路功能解析的研究进展[J]. 实验动物与比较医学, 2025, 45(6): 663-675. DOI: 10.12300/j.issn.1674-5817.2025.147.

DENG Xianming,WANG Fei. Research Progress on Drosophila Electron Microscopy Connectome Database and Functional Analysis of Related Neural Circuits[J]. Laboratory Animal and Comparative Medicine, 2025, 45(6): 663-675. DOI: 10.12300/j.issn.1674-5817.2025.147.

图/表 4

表1 黑腹果蝇电子显微镜连接组数据库的资源信息

Table 1 Resource information of Drosophila melanogaster electron microscopy connectome database

数据库

Databases

访问网页

Web accesses

注释情况

Annotation notes

参考文献

References

一龄幼虫中枢神经系统电子显微镜连接组 (L1 CNS)

L1 larval central nervous system (CNS) electron microscopy connectome

https://l1em.catmaid.virtualflybrain.org

人工追踪所有神经元，共3 016个神经元

[22,32]

成年雌蝇全脑电子显微镜连接组 (FAFB）

Female full adult fly brain electron microscopy connectome

https://fafb.catmaid.virtualflybrain.org

稀疏注释数据库

[29]

FAFB的FlyWire完整注释版

FlyWire fully-annotated version of FAFB

https://codex.flywire.ai/ dataset=fafb

密集注释数据库，共139 255个神经元

[13]

成年雌蝇半脑电子显微镜连接组 (Hemibrain)

Female adult fly hemibrain electron microscopy connectome

https://neuprint.janelia.org

密集注释数据库，共约25 000个神经元

[30]

成年雌蝇腹神经索电子显微镜连接组 (FANC)

Female adult fly nerve cord electron microscopy connectome

https://fanc.catmaid.virtualflybrain.org

密集注释数据库，共约14 600个神经元

[40]

成年雄蝇腹神经索电子显微镜连接组 (MANC)

Male adult fly nerve cord electron microscopy connectome

https://neuprint.janelia.org

https://codex.flywire.ai/ dataset=manc

密集注释数据库，共约23 000个神经元

[39]

成年雌蝇脑及神经索电子显微镜连接组 (BANC)

Female adult fly brain and nerve cord electron microscopy connectome

https://codex.flywire.ai/ dataset=banc

密集注释数据库，共约115 151个神经元

[36]

成年雄蝇中枢神经系统电子显微镜连接组 (maleCNS)

Male adult fly CNS electron microscopy connectome

https://male-cns.janelia.org

https://neuprint.janelia.org

密集注释数据库，共约166 000个神经元

[38]

表1 黑腹果蝇电子显微镜连接组数据库的资源信息

Table 1 Resource information of Drosophila melanogaster electron microscopy connectome database

数据库

Databases

访问网页

Web accesses

注释情况

Annotation notes

参考文献

References

一龄幼虫中枢神经系统电子显微镜连接组 (L1 CNS)

L1 larval central nervous system (CNS) electron microscopy connectome

https://l1em.catmaid.virtualflybrain.org

人工追踪所有神经元，共3 016个神经元

[22,32]

成年雌蝇全脑电子显微镜连接组 (FAFB）

Female full adult fly brain electron microscopy connectome

https://fafb.catmaid.virtualflybrain.org

稀疏注释数据库

[29]

FAFB的FlyWire完整注释版

FlyWire fully-annotated version of FAFB

https://codex.flywire.ai/ dataset=fafb

密集注释数据库，共139 255个神经元

[13]

成年雌蝇半脑电子显微镜连接组 (Hemibrain)

Female adult fly hemibrain electron microscopy connectome

https://neuprint.janelia.org

密集注释数据库，共约25 000个神经元

[30]

成年雌蝇腹神经索电子显微镜连接组 (FANC)

Female adult fly nerve cord electron microscopy connectome

https://fanc.catmaid.virtualflybrain.org

密集注释数据库，共约14 600个神经元

[40]

成年雄蝇腹神经索电子显微镜连接组 (MANC)

Male adult fly nerve cord electron microscopy connectome

https://neuprint.janelia.org

https://codex.flywire.ai/ dataset=manc

密集注释数据库，共约23 000个神经元

[39]

成年雌蝇脑及神经索电子显微镜连接组 (BANC)

Female adult fly brain and nerve cord electron microscopy connectome

https://codex.flywire.ai/ dataset=banc

密集注释数据库，共约115 151个神经元

[36]

成年雄蝇中枢神经系统电子显微镜连接组 (maleCNS)

Male adult fly CNS electron microscopy connectome

https://male-cns.janelia.org

https://neuprint.janelia.org

密集注释数据库，共约166 000个神经元

[38]

图1 黑腹果蝇电子显微镜连接组数据库的发展历程注：黑色圆框标识的是脑区尺度下（左边）和全脑尺度下（右边）黑腹果蝇的各电子显微镜连接组数据库。FAFB，成年雌蝇全脑电子显微镜连接组；Hemibrain，成年雌蝇半脑电子显微镜连接组；FANC，成年雌蝇腹神经索电子显微镜连接组；MANC，成年雄蝇腹神经索电子显微镜连接组；BANC，成年雌蝇脑及神经索电子显微镜连接组；maleCNS，成年雄蝇中枢神经系统电子显微镜连接组。

Figure 1 Development history of Drosophila melanogaster electron microscopy connectome databaseNote： Black circular frames indicate various electron microscopy connectome datasets of Drosophila melanogaster at the brain region scale （left） and the whole brain scale （right）. FAFB， female full adult fly brain electron microscopy connectome； Hemibrain， female adult fly hemibrain electron microscopy connectome； FANC， female adult fly nerve cord electron microscopy connectome； MANC， male adult fly nerve cord electron microscopy connectome； BANC， female adult fly brain and nerve cord electron microscopy connectome； maleCNS， male adult fly CNS electron microscopy connectome.

图2 果蝇视叶结构及运动检测、颜色感知相关的视觉神经元类型（改自文献［55］）

Figure 2 Structure of Drosophila melanogaster optic lobe and types of visual neurons related to motion detection and color perception （adapted from reference ［55］）

图3 雌性果蝇交配、产卵决策的神经环路注：实线表示单级突触连接，虚线表示跨多级的突触连接。红色圆圈、红色线条分别表示抑制性神经元和连接。绿色圆圈、黑色线条分别表示兴奋性神经元和连接。SPSN，性肽感觉神经元；SAG，性肽腹神经节神经元；pC1，pC1中间神经元；pC2l，pC2l中间神经元；aDNs，前背神经元；oviENs，产卵兴奋性神经元；oviINs，产卵抑制性神经元；oviDNs，产卵下行神经元；vpoENs，阴道板展开兴奋性神经元；vpoINs，阴道板展开抑制性神经元；vpoDNs，阴道板展开下行神经元；DNp13，大脑后表面的下行神经元13。

Figure 3 Neural circuits of mating and egg-laying decisions in female DrosophilaNote： Solid lines indicate monosynaptic connections， while dashed lines indicate polysynaptic connections. Red circles and red lines represent inhibitory neurons and connections， respectively. Green circles and black lines represent excitatory neurons and connections， respectively. SPSN， sex peptide sensory neuron； SAG， sex peptide abdominal ganglion neuron； pC1， pC1 interneurons； pC2l， pC2l interneurons； aDNs， anterior dorsal neurons； oviENs， oviposition excitatory neurons； oviINs， oviposition inhibitory neurons； oviDNs， oviposition descending neurons； vpoENs， vaginal plate opening excitatory neurons； vpoINs， vaginal plate opening inhibitory neurons； vpoDNs， vaginal plate opening descending neurons； DNp13， descending neurons 13 on the posterior surface of the brain.

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