“Transformed neurons were recognized as ‘new’ cells, with different properties, by neighboring inhibitory interneurons, which in turn created new circuitry appropriate for their ‘new’ neuronal target,” Arlotta said.

The neuroscientist said that the recent work demonstrates that “synaptic connections among neurons are not made randomly. The brain is much more sophisticated, and different neurons have ways to control the behavior of neighboring circuits in their own unique way to ultimately change how much inhibition, for example, they receive from their synaptic partners.”

The results are important for defining the rules by which neurons in the brain are wired in the first place, but also may provide a way to understand how to rewire the brain in the context of a malfunctioning, pathological circuit. In other words, she said, “Our work shows that, as a neuron, it is important to know who you are, as that will tell your neighbors how to talk with you.”

A parallel approach may involve reprograming the identity of neurons that are already present in the brain, turning them into and thereby replacing neurons that die in disease. For both strategies, the present study suggests that if the new neurons are of the right type, they may be able to direct the building of proper networks with the endogenous cells.

One of the major focuses today in regenerative neurobiology is to use stem cells to produce and replace neurons killed off by disease, and then implant them into patients’ brains. “What we’re talking about is a parallel approach,” Arlotta said. “Instead of making neurons in a dish from stem cells, an alternative would be to reprogram the identity of other neurons that are resistant to disease and turn them directly into the neurons that die in the brain.

“These are early but exciting days,” Arlotta said. “The work thus far has been done in the brains of young mice, which are far more plastic than adult brains,” she pointed out. The next frontier, she said, is to attempt to reprogram neurons and circuits in older brains.

“If we could do it in an adult brain, it would be immensely powerful.”