Brain tissue can incur damage due to degeneration or injury, and one way to repair this is to transplant neurons which will merge with the surrounding tissue and connect with the other neurons in the neighbourhood to make up for the damage. A study carried out by an international collaboration determines the conditions under which neurons implanted in the brain of mice can successfully integrate with the surrounding tissue.
The researchers implanted newly born neurons, taken from the cerebral cortex of mouse embryos into brains of other newborn mice. The cerebral cortex is the region responsible for higher-level functions such as voluntary control of movement and cognition. These embryonic neurons are normally capable of maturing into adult neurons that form long distance connections between parts of the brain. “We optimized the method of transplantation and limited the number of cells that we injected into a recipient brain so that we can analyze these cells individually at a later stage,” Thomas Wuttke, first author of the paper published in Nature Neuroscience says in an email.
The transplanted neurons were labelled with a fluorescent protein (eGFP) which is derived from a species of jellyfish. “Due to labeling, we were able to visualize the transplanted neurons within the brains of the recipient pups and distinguish them from nearby recipient-derived neurons,” says Dr Wuttke.
Experiments showed that the transplanted neurons could form appropriate connections within the brains of the recipient mouse pups when analysed at the level of single cells. “This suggests that by transplanting appropriate types of immature neurons we can potentially reconstruct a neuronal circuitry, at least in the context of a newborn animal,” he adds.
Earlier, pioneering work had shown that neurons implanted in the brain could take root there and also send out long axons (wire-like extensions that help transmit signals) and connect to nearby neurons. However, those experiments were done with bulk transplantation of large numbers of neurons. “Bulk cell experiments are not appropriate for looking at transplanted neurons on a cell-by-cell basis to determine if they mature as required and form correct connections,” says Hari Padmanabhan, co-author of the paper, who is with the Department of Stem Cell and Regenerative Biology, Harvard University.
“This has important implications when we consider transplanting new neurons for correcting diseases caused by neuronal loss that happens either through degeneration or via injury,” he explains.
“We reported, for the first time, that transplanted immature but developmentally ‘primed’ neurons of specific and distinct projection neuron subtypes can integrate cellularly and positionally into postnatal cortex; maintain remarkable fidelity of differentiation and maturation, establish subtype-specific and appropriate long-distance connectivity; and bi-directionally integrate electrophysiologically into local and long-distance circuitry,” says Jeffrey Macklis of harvard University who led the study.
