Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron.
Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron.
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DOI：
10.7554/elife.32373
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发表时间：
2018-04-20
期刊：
影响因子：
7.7
通讯作者：
Grubb MS
中科院分区：
文献类型：
--
作者：
Galliano E;Franzoni E;Breton M;Chand AN;Byrne DJ;Murthy VN;Grubb MS
哺乳动物大脑中的大多数神经发生都是在胚胎期完成的，但在某些区域，神经元的产生在整个出生后的生活中继续。出生后产生的成熟神经元的功能特性通常与胚胎产生的神经元相匹配。然而，我们在这里表明，在嗅球（OB），胚胎和出生后的神经发生产生功能不同的多巴胺能（DA）神经元亚群。我们定义了两个子类的OB DA神经元的存在或不存在的一个关键的亚细胞专业化：轴突起始段（AIS）。大AIS阳性轴突轴承DA神经元只产生于早期胚胎阶段，留下小的轴突AIS阴性细胞作为唯一的DA亚型通过成人神经发生产生。这些群体在功能上是不同的：大的DA细胞更容易兴奋，但表现出较弱的-对于某些长潜伏期或抑制性事件-对气味刺激的反应更广泛。因此，胚胎和出生后的神经发生可以产生不同的神经元亚类，在感觉处理中的成年出生的神经元的功能作用的重要限制。你的大部分脑细胞在你出生之前就已经存在了。但在哺乳动物中，包括人类，其中一些脑细胞，也称为神经细胞或神经元，是在出生后产生的。这些后来产生的神经元通常与子宫中产生的神经元非常相似，而且一旦它们完全成熟，似乎也会发挥类似的作用。然而，还不完全清楚后来产生的神经元是否也有特定的目的。神经元由细胞体和树突组成，细胞体具有被称为轴突的电缆状结构，轴突将信息传递到更远的神经元，树突是从其他神经元接收信息的分支。神经元使用不同的信号分子进行交流，其中一种称为多巴胺，使用这种特定信号的神经元称为多巴胺能神经元。现在，Galliano等人想测试子宫内产生的神经元和出生后产生的神经元是否真的如此相似。为了研究这一点，他们比较了小鼠大脑第一部分中的多巴胺能神经元，以处理有关气味的信息-嗅球。这些特定的神经元具有不同的特性，也可以在出生后产生。Galliano等人研究了它们的发育、形式和用途，发现只有子宫中产生的神经元才能拥有轴突。此外，有轴突的细胞与无轴突的细胞有不同的形式和功能特性，并且在对气味的反应能力上也表现出一些细微的差异。这表明嗅球中两种非常不同类型的多巴胺能神经元在发育过程中的不同阶段产生。更好地了解这些基本的大脑发育特征对于理解大脑如何运作的更广泛目标至关重要，并发现在大脑不正常工作时修复它的方法。特别是出生后产生的神经元，可能使我们能够开发新的治疗策略;例如，添加新的多巴胺能神经元来取代帕金森病等退行性疾病中丢失的神经元。在开发这种再生疗法时，为什么不从大脑如何自然地实现这一目标中吸取教训呢？
Most neurogenesis in the mammalian brain is completed embryonically, but in certain areas the production of neurons continues throughout postnatal life. The functional properties of mature postnatally generated neurons often match those of their embryonically produced counterparts. However, we show here that in the olfactory bulb (OB), embryonic and postnatal neurogenesis produce functionally distinct subpopulations of dopaminergic (DA) neurons. We define two subclasses of OB DA neuron by the presence or absence of a key subcellular specialisation: the axon initial segment (AIS). Large AIS-positive axon-bearing DA neurons are exclusively produced during early embryonic stages, leaving small anaxonic AIS-negative cells as the only DA subtype generated via adult neurogenesis. These populations are functionally distinct: large DA cells are more excitable, yet display weaker and – for certain long-latency or inhibitory events – more broadly tuned responses to odorant stimuli. Embryonic and postnatal neurogenesis can therefore generate distinct neuronal subclasses, placing important constraints on the functional roles of adult-born neurons in sensory processing. Most of your brain cells were born before you were. But in mammals, including humans, some of these brain cells, also known as nerve cells or neurons, are created after birth. These later-generated neurons are often extremely similar to their counterparts produced in the womb, and also seem to perform a similar role once they are fully mature. However, it has not been entirely clear if the later-produced neurons may also have a specific purpose. Neurons are made of a cell body with a cable-like structure called axon that transmits information to more distant neurons, and dendrites, which are branches that receive information from other neurons. Neurons use different signalling molecules to communicate, one of which is called dopamine, and the neurons that use this specific signal are called dopaminergic neurons. Now, Galliano et al. wanted to test if neurons created in the womb, and neurons created after birth, are really so similar. To investigate this, they compared the dopaminergic neurons from mice found in the first part of the brain to process information about smell – the olfactory bulb. These specific neurons are known to have diverse properties and can also be produced after birth. Galliano et al. studied their development, form and purpose, and discovered that only neurons produced in the womb can possess an axon. Moreover, the axon-bearing cells had a different form and functional properties to their axon-less cousins, and also showed some subtle differences in their ability to respond to smell. This demonstrates that two very different types of dopaminergic neurons in the olfactory bulb are produced at different stages during the development. A better knowledge of such basic brain-developmental features is essential for the wider goal of understanding how the brain operates, and to discover ways to repair it when it is not working properly. Neurons created after birth in particular, might enable us to develop new treatment strategies; for example, adding new dopaminergic neurons to replace those lost in degenerative disorders such as Parkinson’s Disease. When developing such regenerative therapies, why not learn lessons from how the brain can achieve this naturally?