Function and regeneration of dopaminergic neurons in the brain of zebrafish

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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.