神经图的布线特异性如何在发育过程中出现?成年果蝇嗅觉肾小球图的形成始于p早期投影神经元(PN)树突的图案化。为了更好地理解这张地图的布线特异性的起源,我们创建了遗传工具,以PN型特异性分辨率系统地表征整个发育过程中的枝晶图案。我们发现PNs组合使用谱系和出生顺序来构建初始树突图。具体来说,出生顺序指导树突以旋转和二元方式瞄准前臭和侧向谱系的PN,分别。基于双光子和自适应光学晶格光片显微镜的延时成像显示,PN树突在几秒钟的时间范围内通过方向依赖性分支稳定启动主动瞄准。此外,幼虫和成虫嗅觉回路中使用的PN修剪其幼虫特定的树突,并同时重新扩展新的树突,以促进及时的嗅觉图组织。我们的工作强调了特定类型的神经元访问和延时成像在识别构成功能神经图复杂模式的布线机制方面的力量和必要性。
大脑的感知能力,行动和记忆依赖于神经元之间复杂的连接网络。将这些连接组织成神经图对于处理感官信息至关重要。例如,不同的气味由大脑中被称为嗅球的特定神经元代表,允许动物区分气味。嗅球中的投影神经元具有称为树突的延伸,可接收来自感觉神经元的信号。科学家广泛使用成年果蝇的嗅觉图来研究大脑布线,因为它们的感觉和投射神经元之间存在特定的联系。这导致在哺乳动物中发现了类似的布线策略。但是,在开发过程中如何形成嗅觉图还没有完全了解。为了调查,Wong等人。建立了遗传工具来标记特定类型的嗅觉投射神经元在果蝇发育期。这表明一组投影神经元根据它们出生的顺序以顺时针旋转的方式引导它们的树突:第一个出生的神经元向触角叶的右上方发送树突(果蝇相当于嗅球),最后一个出生的人把树突送到左上方。Wong等人。还对实验室中生长的活体大脑进行了高分辨率延时成像,以确定树突如何做出布线决定。这表明投射神经元向各个方向发送树突,但优先稳定那些在神经元最终瞄准的方向上延伸的。此外,实时成像显示神经元可以同时去除旧的树突(用于幼虫)和构建新的树突(用于成虫),允许他们快速创建新电路。这些实验证明了对特定类型的神经元进行成像以了解在发育中的大脑中组装神经图的机制的价值。进一步的工作可以使用Wong等人创建的遗传工具。为了研究特定基因如何在这个和其他神经图谱中决定布线决策,有可能对与布线缺陷相关的神经系统疾病产生见解。
How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with the patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.
The brain’s ability to sense, act and remember relies on the intricate network of connections between neurons. Organization of these connections into neural maps is critical for processing sensory information. For instance, different odors are represented by specific neurons in a part of the brain known as the olfactory bulb, allowing animals to distinguish between smells. Projection neurons in the olfactory bulb have extensions known as dendrites that receive signals from sensory neurons. Scientists have extensively used the olfactory map in adult fruit flies to study brain wiring because of the specific connections between their sensory and projection neurons. This has led to the discovery of similar wiring strategies in mammals. But how the olfactory map is formed during development is not fully understood. To investigate, Wong et al. built genetic tools to label specific types of olfactory projection neurons during the pupal stage of fruit fly development. This showed that a group of projection neurons directed their dendrites in a clockwise rotation pattern depending on the order in which they were born: the first-born neuron sent dendrites towards the top right of the antennal lobe (the fruit fly equivalent of the olfactory bulb), while the last-born sent dendrites towards the top left. Wong et al. also carried out high-resolution time-lapse imaging of live brains grown in the laboratory to determine how dendrites make wiring decisions. This revealed that projection neurons send dendrites in all directions, but preferentially stabilize those that extend in the direction which the neurons eventually target. Also, live imaging showed neurons could remove old dendrites (used in the larvae) and build new ones (to be used in the adult) simultaneously, allowing them to quickly create new circuits. These experiments demonstrate the value of imaging specific types of neurons to understand the mechanisms that assemble neural maps in the developing brain. Further work could use the genetic tools created by Wong et al. to study how wiring decisions are determined in this and other neural maps by specific genes, potentially yielding insights into neurological disorders associated with wiring defects.