BioEd Online

Electrodes inserted into certain parts of the brain — in a technique known as deep brain stimulation — can stimulate the growth of new neurons that are used in memory formation, according to research in mice.

The findings show that artificially created neurons can be fully functional — a topic of hot debate in the neuroscience community. Knowing that the cells are functional, rather than just useless growths, is a boost for those seeking to use the treatment against Alzheimer's disease and other memory-degeneration disorders. "I'm hoping to help people who have difficulty remembering things," says Scellig Stone, a neurosurgery resident and PhD candidate at the University of Toronto.

One of Stone's supervisors, Paul Frankland of the Hospital for Sick Children in Toronto, presented the results at the annual meeting of the Canadian Association for Neuroscience in Vancouver, Canada, on 25 May. In his study, Stone electrically stimulated part of the limbic system in the brains of mice for an hour. Rodent brains normally produce thousands of new neurons a day; by 3–5 days after the procedure, the electrical stimulation had doubled that. During this time of high neuron growth, the team injected the mice with iododeoxyuridine to label the newly formed cells.

Six weeks after the stimulation, the mice were trained to find a platform hidden underwater in a swimming tank. Once the researchers were convinced the mice had learned the task, they examined their brains, looking for a protein called Fos. Fos is produced only by active cells, and takes around 90 minutes to form, so the team could time their examination to pinpoint neurons that had been used explicitly in the memory task. They found that the new neurons had the same level of Fos and were therefore just as active as other, older neurons. "These new neurons aren't just sitting around doing nothing," says Stone.

Turning back the clock

The mice used in Stone's experiment didn't have a memory impairment to begin with, so it's unlikely that their memory would have improved from the neuron growth. But researchers assume that the growth of new, functional neurons in mice or people with dementia or other brain degenerative problems would help them. There could be complications, however, Frankland admits. "You might erase old memories, but become capable of making more memories," he explains.

Frankland's team has also looked at a few elderly 2-year-old mice, and found that deep brain stimulation boosted their neuron growth by eight times their normal rate. This rate of growth is similar to that seen in 2-month-old mice, suggesting that their mental functions could be rejuvenated by the procedure. However, the researchers haven't yet tested the older mice to see if they are better at making memories.

"The reason why it's so exciting is it's potentially a neuro-regenerative or restorative therapy," says Stone.

"He has an interesting technical advance," says Brian Christie of the University of Victoria in Canada, who heard Frankland's talk. "Now we can really see what neurogenesis is doing." Previous methods for looking at the activity of artificially induced neurons — including chopping them out and seeing what happens — have yielded inconclusive results.

Previous studies have shown increased learning ability in animals after tasks such as exercise, for example, which is also known to help boost neuron growth. But it's hard to tell if the memory boost in these studies came directly from the new neurons, or from some other change in brain chemistry, notes Christie. Frankland's work is a big step forward, he says, because it helps to sort out exactly what is going on in the new neurons.

How do your neurons grow?

More than 55,000 people are currently receiving deep brain stimulation as treatment for various disorders. Most of these patients are being treated for Parkinson's disease, and as the electrodes activate a part of the brain that controls motor function, the technique is not expected to prompt the growth of new neurons. But patients being treated for depression, epilepsy and some other conditions do have the electrodes placed in circuits expected to prompt neuron growth.

Another of Stone's supervisors, Andres Lozano, has six patients in an early-stage trial of deep brain stimulation for Alzheimer's disease. This was prompted by another, accidental discovery, in which a patient who was undergoing deep brain stimulation for an obesity disorder started recalling vivid memories (see 'Brain electrodes can improve learning'). That memory effect was different: it was instantaneous, and therefore not caused by the formation of new neurons. But as patients with electrodes in this part of the brain are expected to sprout new neurons too, the trial could be used to study whether the new neurons become involved in memory formation, as they do in mice. Lozano expects the first results in August.