Transplanted embryonic neurons can be incorporated into an existing network, in mice, and correctly carry out the tasks of damaged cells originally found in that region, researchers at the Max Planck Institute of Neurobiology in Martinsried, the Ludwig Maximilians University Munich and the Helmholtz Zentrum München have shown.

When it comes to recovering from damage, the adult human brain has very little ability to compensate for nerve-cell loss. So biomedical researchers and clinicians are exploring the possibility of using transplanted nerve cells to replace neurons that have been irreparably damaged as a result of trauma or disease.

However, it was not previously clear whether transplanted neurons can be integrated sufficiently, to result in restored function of the lesioned network.

Embryonic Neurons Transplantation

Neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease lead to a loss of brain cells, as do stroke or certain injuries. The mammalian brain can replace these cells only in very limited areas, making the loss in most cases a permanent one.

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, if the nerve cells transplanted in such studies help to overcome existing network gaps or whether they actually replace the lost cells, remained unknown.

In the current study, researchers specifically asked whether transplanted embryonic nerve cells can functionally integrate into the visual cortex of adult mice.

Mark Hübener, who co-lead the study along with Magdalena Götz, explains:

“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."

Two-photon Microscopy

In their experiments, the team transplanted embryonic nerve cells from the cerebral cortex into lesioned areas of the visual cortex of adult mice. Over the course of the following weeks and months, they monitored the behavior of the implanted, immature neurons by means of two-photon microscopy to ascertain whether they differentiated into so-called pyramidal cells, a cell type normally found in the area of interest.

Hübener says:

“The very fact that the cells survived and continued to develop was very already encouraging."

But 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.

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.

Susanne Falkner et al. Transplanted embryonic neurons integrate into adult neocortical circuits Nature (2016). DOI: 10.1038/nature20113

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

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