Transplanted embryonic nerve cells could functionally integrate into damaged neural networks in mice

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It is a difficult task to save the neurons in the adult human brain that have got damaged due to trauma or disease, as the brain has very little ability to compensate for nerve-loss. Therefore it would be a boon, if you could transplant nerve cells that could replace the damaged neurons and possibly restore function.

A new study by researchers at the Max Planck Institute of Neurobiology in Martinsried, the Ludwig Maximilians University Munich and the Helmholtz Zentrum München is trying to demonstrate precisely that, in mice.

Many neurodegenerative diseases such as Alzheimer’s, Parkinson’s disease, stroke or even certain injuries lead to a loss of brain cells. In most cases, the loss is a permanent one due to the post- mitotic nature of neurons and their inability to regenerate.

The transplantation of young nerve cells into an affected network of patients for example with Parkinson’s disease, allow for the possibility of a medical improvement of clinical symptoms. However, it was not known whether the nerve cells transplanted in such studies helped to overcome existing network gaps or whether they actually replace the lost cells.

In a joint study, researchers of the Max Planck Institute of Neurobiology, the Ludwig Maximilians University Munich and the Helmholtz Zentrum München have specifically asked whether transplanted embryonic nerve cells can functionally integrate into the visual cortex of adult mice.

 “This brain region is ideal for such experiments,” says Magdalena Götz, joint leader of the study together with Mark Hübener, who continues to explain: “By now, we know so much about the functions of the nerve cells in the visual cortex and the connections between them that we can readily assess whether the new nerve cells actually perform the tasks normally carried out by the network.”

In their experiments, the team transplanted embryonic nerve cells from the cerebral cortex into damaged areas of the visual cortex of adult mice. Through two-photon microscopy, they monitored the behaviour of the implanted, immature neurons over weeks and months and assessed if it did, differentiate into the so-called pyramidal cells, that was typical of that region.

“The very fact that the cells survived and continued to develop was already encouraging,” Hübener remarks.

Things got really exciting when the scientists took a closer look at the electrical signals of the transplanted cells. In their joint study, PhD student Susanne Falkner and Postdoc Sofia Grade were able to show that the new cells formed the synaptic connections that neurons in their position in the network would normally make, and that they responded to visual stimuli.

Neuronal transplants (blue) connect with host neurons (yellow) in the adult mouse brain in a highly specific manner, rebuilding neural networks lost upon injury. Courtesy: © Sofia Grade (LMU/Helmholtz Zentrum München)
Neuronal transplants (blue) connect with host neurons (yellow) in the adult mouse brain in a highly specific manner, rebuilding neural networks lost upon injury. Courtesy:
© Sofia Grade (LMU/Helmholtz Zentrum München)

The team then went on to characterize, for the first time, the precise pattern of connections made by the transplanted neurons.

Astonishingly, they found that pyramidal cells derived from the transplanted immature neurons formed functional connections with the appropriate nerve cells all over the brain. In other words, they received precisely the same inputs as their predecessors in the network.

In addition, the cells were able to process that information and pass it on to the correct downstream neurons.

“These findings demonstrate that the implanted nerve cells have integrated with high precision into a neuronal network into which, under normal conditions, new nerve cells would never have been incorporated,” explains Götz, whose work at the Helmholtz Zentrum and at the LMU focuses on finding ways to replace lost neurons in the central nervous system.

The new study reveals that the adult mammalian brain is able to retain its ability to regenerate with the aid of transplanted, immature neurons, which are capable of closing functional gaps in an existing neural network.

Source: Max-Planck