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

一个健康的大脑需要其组成细胞或神经元彼此正确连接。这些连接可能涉及数千个不同的输入到达单个细胞，然后该细胞整合传入的信息并向一系列高度特定的下游伙伴发送输出信号。通过这种方式，神经网络将输入信息转换为经过适当处理的输出信号，这样，例如，感官体验就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。对于一种特殊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。这些细胞只占绝大多数，因为我们的大多数神经元是在出生前产生的，在受伤或患病后缺乏再生能力。然而，在成熟哺乳动物大脑的一些特殊区域，新的神经元在整个生命过程中不断产生，这一过程被称为成人神经发生。这会产生全新的神经元，这些神经元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。我们的建议的目标是研究这些新形成的连接，这些连接是由一种特殊类型的成人生成的神经元形成的。在嗅球中——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早期阶段对调节感觉信号起着关键作用，这些细胞可以在一生中不断产生。然而，我们完全不知道这些神经元的输入和输出连接以及回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种感觉处理回路中产生具有独特连接的细胞。在解决这个重要的基本生物学问题时，我们的工作有可能对英国的医疗保健产生影响。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，至少影响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失去的疾病的治疗提供信息，比如帕金森氏病。我们对旧电路中新神经元的研究有更广阔的前景，可以通过向受干扰的神经网络中添加新生成的细胞来修复脑损伤。

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.