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Distinct connectivity of newly-generated dopaminergic neurons in the adult brain?

成人大脑中新生的多巴胺能神经元的独特连接性？

基本信息

批准号：
BB/N014650/1
负责人：
Matthew Grubb
金额：
$ 47.09万
依托单位：
King's College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN014650%2F1
关键词：
Distinct connectivity newly generated dopaminergic

项目摘要

A healthy brain requires its constituent cells, or neurons, to be properly connected to each other. These connections can involve thousands of different inputs arriving onto a single cell, before that cell integrates the incoming information and sends an output signal to a range of highly specific downstream partners. In this way, neuronal networks transform input information into a suitably-processed output signal, so that sensory experience, for example, can control our behaviour. Understanding the way in which neurons are connected, then, is crucial in understanding their function. This is particularly true for a unique type of neuron: those born in the adult brain. These cells are in the great minority, because most of our neurons are generated before birth and lack the ability to regenerate after injury or disease. However, in a few specialised zones of the mature mammalian brain, new neurons are continually produced throughout life in a process known as adult neurogenesis. This generates entirely new neurons which must integrate into existing networks, receiving inputs and sending outputs to contribute to circuit function.The goal of our proposal is to study these newly-formed connections made by a particular type of adult-generated neuron. In the olfactory bulb - the first part of the brain to process smell information arriving from the nose - dopaminergic neurons play a key role in modulating sensory signals at their earliest stages, and these cells can be generated throughout life. However, it is entirely unknown whether the input and output connections, and therefore the circuit function of these neurons, is unique to dopaminergic cells produced in adulthood. By using a combination of cutting-edge approaches, we will ask whether adult neurogenesis produces cells with unique connectivity in this sensory-processing circuit.In addressing this important basic biological question, our work has the potential to impact on healthcare in the UK. Our study of the olfactory system may inform future approaches to treat debilitating smell disorders such as anosmia and hyposmia, which have a huge impact on quality of life and affect at least 20% of the population. Our focus on dopaminergic neurons may inform treatments for disorders where these cells are lost in later life, such as Parkinson's Disease. And our study of new neurons in old circuits has the wider promise of informing any attempt to repair brain damage by adding freshly-generated cells to perturbed networks.

一个健康的大脑需要其组成细胞或神经元相互正确连接。这些连接可能涉及到达单个细胞的数千个不同输入，然后该细胞整合传入信息并将输出信号发送到一系列高度特定的下游合作伙伴。通过这种方式，神经元网络将输入信息转换为适当处理的输出信号，因此感官体验可以控制我们的行为。因此，了解神经元的连接方式对于理解它们的功能至关重要。对于一种独特类型的神经元来说尤其如此：那些出生在成人大脑中的神经元。这些细胞是极少数，因为我们的大多数神经元是在出生前产生的，在受伤或疾病后缺乏再生能力。然而，在成熟哺乳动物大脑的一些专门区域中，新的神经元在整个生命过程中不断产生，这一过程被称为成年神经发生。这产生了全新的神经元，它们必须整合到现有的网络中，接收输入并发送输出，以促进电路功能。我们建议的目标是研究这些由特定类型的成人生成的神经元形成的新连接。在嗅球-大脑处理来自鼻子的气味信息的第一部分-多巴胺能神经元在其最早阶段调节感觉信号中起着关键作用，并且这些细胞可以在整个生命中产生。然而，目前还完全不清楚这些神经元的输入和输出连接以及电路功能是否是成年期产生的多巴胺能细胞所独有的。通过使用尖端方法的组合，我们将询问成人神经发生是否在这个感觉处理电路中产生具有独特连接性的细胞。在解决这个重要的基本生物学问题时，我们的工作有可能影响英国的医疗保健。我们对嗅觉系统的研究可能会为未来治疗嗅觉障碍（如嗅觉缺失和嗅觉减退）的方法提供信息，这些疾病对生活质量有巨大影响，影响至少20%的人口。我们对多巴胺能神经元的关注可能会为这些细胞在晚年丢失的疾病（如帕金森病）的治疗提供信息。而我们对旧回路中新神经元的研究，更有希望为任何试图通过向受干扰的网络添加新生成的细胞来修复脑损伤的尝试提供信息。