The brain of a songbird provides a fascinating window into learning and memory, and it may hold the key to new therapies for neurological disease and injury, MIT neurobiologist Carlos Lois’ groundbreaking research shows.

All adult mammals, including humans, have a limited ability to replace brain cells after they are lost to disease or injury, as these cells grow in scant numbers in only two small regions of the brain. The songbirds that Lois studies are different. As juveniles learning to sing, and later as adults composing new songs, they regenerate multitudes of brain cells, or neurons, every year. Lois hopes to decode the genetic programs behind this astonishing capability in the hope that it may one day be harnessed to replace the neurons lost to Alzheimer’s, Parkinson’s, stroke, and paralysis.

“Most songbirds, when they are born, cannot sing. Like humans, they learn to sing by listening to an adult,” says Lois, a principal investigator in the Picower Center for Learning and Memory and a professor of brain and cognitive science. As the birds practice their tunes, the neurons in the “song center” of their brains greatly increase. More remarkably, Lois discovered, these new cells migrate freely throughout the brain, searching for appropriate connections with established neurons.

Lois, who studied medicine in his native Spain before pursuing a Ph.D. in neurobiology in the U.S., was the first to show that long-distance cell migration, familiar in embryonic brain development, also occurs in adult brains (and to an exceptional degree in songbirds). Now, he focuses on just how those newly generated, mobile cells manage to integrate with pre-existing neural circuits without disrupting millions of already functioning synapses, or connections between brain cells. This is an extremely fine-tuned process akin to inserting a new memory card in a running computer — without crashing the system.

“Not only do these cells manage to navigate through the very packed brain without disrupting the function of the pre-existing neurons, they also have almost complete freedom to just move around. They seem to be sampling the environment through which they travel,” he says.

As part of his research, Lois has developed ingenious techniques to study the function of brain cells. For example, through genetic manipulation he “labels” newly generated neurons involved in a songbird’s capacity for singing, then uses a sophisticated imaging method to observe those cells in action. “We can actually see the neurons moving through the brain when the animal is alive, and we can follow individual neurons day after day for long periods of time, up to one month,” he says.

He also genetically alters the electrical signaling properties of new neurons, in this case in the brain of the more commonplace lab mouse. The approach allows him to test how these cells communicate with other neurons as they quite literally wander in search of viable connections.

These experiments provide valuable clues as Lois pursues his ultimate goal: understanding the genetic mechanisms behind the process of neural regeneration. He is working toward using a breakthrough genetic engineering technique that he invented earlier in his career to precisely control the formation and behavior of new neurons in songbirds. He could thus determine the cells’ role in memory and learning, with an eye toward translating their powerful properties to stem cell-based therapies for brain cell loss and damage in humans.

“The main problem with any kind of stem cell treatment for brain diseases in humans is that two complex things must occur: You need the cells to move so that they find their target; and you need them to make very specific contacts with existing cells.”

With these amazing discoveries, Lois is gaining ground toward that feat.