Function and regeneration of dopaminergic neurons in the brain of zebrafish

成年斑马鱼具有惊人的修复大脑和脊髓损伤的能力。特别是，大脑中有所谓的祖细胞，它们可以分裂，从而产生新的神经细胞。在包括人类在内的哺乳动物中，这种再生通常失败。产生化学多巴胺的神经细胞是大脑活动的重要调节剂，特别容易受到毒素，衰老和疾病的影响，例如帕金森氏病，导致终身残疾。我们计划确定成年斑马鱼中产生多巴胺的神经细胞是否再生，以及这种修复是否导致失去的功能恢复。这将表明新的神经细胞在大脑网络中建立了有用的连接。重要的是，我们将阐明在再生过程中被激活的基因，以及哪些分子信号诱导斑马鱼的祖细胞产生产生多巴胺的神经细胞。特别是，我们将开发药理学和遗传学工具，以跟踪这些细胞随时间的再生。这将帮助我们从根本上确定如何在成人和完全连接的神经系统中替换丢失的神经细胞。此外，许多分子信号和祖细胞也存在于哺乳动物的大脑中，因此我们的项目也将揭示哺乳动物中缺失的特定机制，以实现退化神经细胞的成功替代。

Adult zebrafish have an amazing capacity to repair injuries to their brain and spinal cord. In particular, there are so-called progenitor cells in the brain that can divide and thus generate new nerve cells. In mammals, including humans, such regeneration usually fails. Nerve cells that produce the chemical dopamine, an important modulator of brain activity, are particularly vulnerable to influences of toxins, aging and disease, such as Parkinson's disease which leads to life-long disability. We plan to determine whether dopamine producing nerve cells are regenerated in the adult zebrafish and whether this repairs leads to recovery of lost functions. This would show that new nerve cells make useful connections in the brain network. Importantly, we will elucidate the genes that are activated during regeneration and which molecular signals induce progenitor cells to generate dopamine producing nerve cells in zebrafish. In particular, we will develop pharmacological and genetic tools to follow regeneration of these cells over time. This will help us determine at a fundamental level how it is possible to replace lost nerve cells in the adult and fully wired nervous system. Moreover, many of the molecular signals and progenitor cells are also present in the brain of mammals, such that our project will also shed light on the specific mechanisms missing in mammals to achieve successful replacement of degenerating nerve cells.