Despite its small size—it could sit in the palm of your hand—the zebra finch is a remarkable learner. A songbird native to Australia, it's renowned for its ability to pick up new songs.
That talent has made it a favorite of scientists studying how animal brains imprint new skills, particularly vocal learning, or the capacity to perfect new sounds. And now researchers at Boston University have discovered another quirk to the zebra finch brain—one that could also have implications for understanding our own gray matter.
In a study that looked at the bird's brain in unprecedented detail, they uncovered new insights into a mechanism known as neurogenesis—the birth, migration, and maturation of neurons—that may help the brain learn, add new skills, and restore and repair itself.
Observing the finch brain using a high-powered microscope, the researchers watched as new neurons bullied their way through the brain en route to bolstering existing circuits and connections. They'd expected the neurons to gingerly step around established brain structures, including more mature brain cells, to better preserve them; instead, they saw them tunnel right through, squishing and shoving as they went.
According to the BU-led team, their findings could help explain human vulnerability to a range of brain disorders. They also noted that cell tunneling is used by some metastatic cancer cells. The findings were published in Current Biology.
"We found that in songbirds, new neurons in the adult brain behave like explorers forging a path through a dense jungle," says Benjamin Scott , a BU College of Arts & Sciences assistant professor of psychological and brain sciences and the study's corresponding author. That may help them learn new things or repair damage, but it could come with a cost to existing cells and memories—and that might be why neurogenesis is a skill humans don't seem to have beyond the womb.
"This potentially disruptive behavior may help explain why humans and other mammals have limited capacity to regenerate brain tissue in adulthood," says Scott, "leaving us more vulnerable to neurodegenerative disorders such as Alzheimer's disease."
Tunneling Neurons
When you're born, your brain pretty much has all the neurons it's ever going to have. Other organs—from your skin to your heart—might get frequent cell updates, but the brain is working on version 1.0.
That's true for most mammals, but not fish, reptiles, and birds—their brains get a regular refresh.
"This raises two questions," says Scott, who's also affiliated with BU's centers for neurophotonics, photonics, and systems neuroscience. "Why do other species have high rates of neurogenesis throughout life and why is it so restricted in humans? And is there something we can learn from their biology that we might be able to harness in future?"
Scott typically studies the neural circuits that control behavior in humans and other mammals, but chose the zebra finch to investigate neurogenesis because it has a reputation as a champion species—it's really good at generating new neurons.
"We applied a new tool to study this process [neurogenesis] called electron microscopy-based connectomics—basically a really high-powered microscope—to image these cells at a very high resolution," says Scott. "Our first hope was just to say, what does this look like at a detail we couldn't see before?" Instead, they spotted the tunneling neurons.
If these new neurons are deforming brain tissue, says Scott, are they also disrupting memories along the way? And, if neurogenesis comes with a cost, how does that balance against the brain's capacity for learning new things and repairing after injury?
Scott has two—as yet untested—hypotheses for what the findings might mean for the human brain. The first is that our brains evolved to limit neurogenesis after birth as a form of protection—a way of making sure determined neurons couldn't barge through mature connections and damage memory storage.
"There is an alternative framing that is more optimistic," he says. "Our discovery of tunneling shows how cells can move without glia scaffolds." These are the structures that operate as highways for migrating neurons.
"Most glia scaffolds are lost in humans after birth, and this loss was thought to be an obstacle for neurogenesis in the adult brain," says Scott. "However, our work shows that new neurons in the bird do not need this glia scaffold. This is exciting because it means that brain repair may not require specialized glia scaffolds." That opens the door for scientists to explore potential stem-cell therapies that would spark neurogenesis in humans.
Next: Figuring Out the How and Why of Neurogenesis
In current studies, Scott and the team in his BU Laboratory of Comparative Cognition are digging into the biology driving neurogenesis to uncover which genes are regulating the process. Much of the work merges ideas and tools from biomedical engineering and neuroethology, the study of the mechanisms underpinning animal behavior.
"Right now, we're using a technique called single-cell RNA sequencing to identify genes that are expressed by these new neurons as they migrate," says Scott. "We want to know what other cells they're talking to as they move and how they are speaking to these different cells."
That'll help them figure out whether neurons warn other cells they're travelling through and how they know where to stop and integrate with a current circuit.
"We share a lot with our animal relatives on this planet," says Scott. And, while the term "bird brain" might be an insult, by learning more about the biology of songbird brains, he says, we could learn some remarkable things about our own.
This research was funded with support from the BU Neurophotonics Center. The study also included researchers from the MRC Laboratory of Molecular Biology, United Kingdom, and the Max Planck Institute for Biological Intelligence, Germany.
