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Dopaminergic cells are important for controlling voluntary movement and emotions such as motivation and reward that drive behavior. They are often lost in movement disorders like Parkinson’s disease. Many neuroscientists are interested in the therapeutic potential of creating new dopaminergic cells.
They injected a viral vector to express a cocktail of proteins into the striatum, a region of the brain rich in GABAergic neurons that help control muscle movement. The cocktail consisted of three transcription factors, NURR1, FOXA2, and LMX1A, which help decode genetic instructions for building dopaminergic neurons.
The mice were also treated with valproic acid, which was previously shown to play a role in cell reprogramming. The team targeted glial cells due to their ability to regenerate and multiply more readily than neurons, theoretically making them better therapeutic candidates.
But when they looked at the brain slices of the injected mice, they found the glia unchanged. Instead, some GABAergic medium spiny neurons cells that are directly controlled by dopaminergic neurons had transformed. The new cells appeared to behave more like native dopaminergic neurons, although they also retained residual features of the medium spiny neurons.
They showed rhythmic activity and formed network connections similarly to dopaminergic cells, as the researchers discovered through electrode recordings and reporter assays. Subsequent immunohistochemistry and reporter assays revealed that the new cells sprung from mature medium spiny neurons without passing through a proliferative progenitor stage.