When neurons are born determines what they can become

In terms of royalty, things are clear: the first child of the monarch inherits the crown. Siblings born later have to settle for a less glamorous profession. This is quite similar for certain nerve cells in the brain. In their case, it is not the order in which they were born, but at least the timing of their emergence that determines their future career. This is shown by a recent study by the University of Bonn. The results were obtained in mice so the extent to which they can be transferred to humans is still uncertain. They have now been published in the journal eNeuro.

In their study, the researchers looked at a specific type of cell: dopamine neurons in the midbrain. They owe their unwieldy name to their ability to produce dopamine. This messenger compound plays an essential role in signal transmission between certain nerve cells. The loss of dopaminergic neurons can therefore lead, for example, to Parkinson’s disease, with its characteristic deficits in the sequences of movements.

Dopaminergic neurons in the midbrain are not all the same . “We now know of a whole range of different forms, all of which most likely perform specific tasks in the brain,” says Professor Dr. Sandra Blaess of the Institute for Reconstructive Neurobiology at the University Hospital Bonn. “They send very long nerve fibers, called axons, to different areas of the brain. One of the things they transport via these fibers to the respective target region is dopamine.” Nevertheless, most of these varieties probably come from the same progenitor cells. “We wanted to know how these progenitors develop into different groups of dopaminergic cells without which the brain would not function.”

The moment of emergence determines the career path

It has been known for some time that the career of other nerve cells depends on the moment of their emergence. “We tried to find out whether this was also the case in dopaminergic neurons,” explains Alessandro Petese, who is doing his doctorate in Professor Blaess’s group. “In mice, it takes four to five days for all the progenitor cells to convert into dopaminergic neurons. We wanted to know: Are the neurons that form on the first day different from those that form on the second, third or fourth day?

To do this, the researchers labeled the precursor cells at different times so that all neurons that emerged from these precursors in the following days would light up green under the microscope. In contrast, neurons that had previously emerged from unlabeled precursors remained dark. “In this way, we discovered that cells born early can still develop into all styles of dopaminergic neurons in the midbrain,” says Blaess collaborator Franca Fries. In a figurative sense, these cells can therefore still follow very different career paths. “However, the later they are born, the narrower their selections become. They therefore become more specialized.”

Basic research relevant to practice

The research group now wants to study which signals force progenitor cells more and more into a certain race. “In reconstructive neurobiology, efforts are currently being made to create neurons from stem cells,” says Blaess, who is also a member of the transdisciplinary research area “Life and Health” at the University of Bonn. “That’s because it allows targeted reproduction of nerve cell styles in the lab, which could potentially be used to reverse the cell loss that occurs in Parkinson’s disease, for example.” To do this, it is crucial to understand the processes that take place during natural differentiation.

The results of the study could also make it possible to specifically inhibit certain types of cells dopaminergics in mice. This may provide new insights into the mechanisms of various diseases in which alterations in the dopamine system play a role – from depression to schizophrenia to Parkinson’s disease.

Funding:

The study was funded by the German Research Foundation (DFG) and the Maria von Linden Program at the University from Bonn.

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