The perineuronal net is known to play a crucial role in memory. This structure surrounds certain neurons, encasing their synapses, protecting them and preventing changes. This way, our brains can retain profound memories and patterns, engraining them into us. But this can also make them less adaptable. Researchers have now suggested that there are ways to remove the perineuronal net, which could restore the brain's youthful flexibility.
Microglia cells are known to play an important role in immunity in the brain. They're able to absorb synapses or whole neurons, which is sometimes seen in late-stage Alzheimer's disease. About four years ago, the team of neuroscientist Sandra Siegert at IST Austria were working with mice that had been anesthetized with ketamine, and they found that the drug caused the animals' microglia cells to become very active.
"The strong response of the microglia upon ketamine anesthesia surprised us," noted Alessandro Venturino, a researcher in the Siegert lab. "But we did not see any synapses or dead neurons vanishing. So, we were puzzled, what the microglia were actually eating."
The scientists were stunned when they discovered that the microglia were destroying the perineuronal net. Ketamine is a general anaesthetic agent and has recently proven to be useful as a psychiatric drug.
"Alessandro came to my office and told me that the perineuronal net was gone. I could not believe it," said Siegert. "After just three treatments, we could see a considerable loss in the perineuronal net, which lasted for seven days before being rebuilt."
Neurons communicate using electrical signals that are sent to and from each other and other cells. In the brain, coordinated impulses of these signals, brain waves, can be affected by external stimuli, like certain wavelengths of light when shined into the eyes. The researchers found that a specific wavelength of light had the same effect as ketamine. These findings have been published in Cell Reports.
"It had been previously shown that light flickering 40 times a second (at 40 hertz) can promote microglia to remove plaques in Alzheimer disease. But it did not remove the perineuronal net. This fine-tuning between distinct brainwaves and the microglia action is the most fascinating and might be a new way of thinking about brainwaves," said first study author Venturino.
This research presents two potential non-invasive approaches for removing the perineuronal net, something which would otherwise be extremely risky and have long-term effects. It remains to be seen whether ketamine or 60-hertz light flickers will have a positive impact on the human brain.
If the perineuronal net can be reduced, neurons might be open to new input and able to generate new synapses. This could be a way to overcome traumatic experiences, which are often relived in disorders like PTSD, and not as a way to make people hyper intelligent, the researchers cautioned. It's also a technique that still has to be tested for safety and efficacy.
"But we are very cautious because in this formative window also something traumatic could happen," Siegert noted. "It is probably also not a good idea to blast yourself with flickering light."