Scientists Coax Precursor Cells to Replace Neurons in Adult Zebra Finches
Boston, MA -- February 22, 2000 -- A little bird told Jeffrey Macklis that it might be possible, one day, to awaken the birth of new neurons inside a person's brain without transplantation of so-called stem cells from other sources.
In the February Neuron, Macklis, a neuroscientist at Boston's Children's Hospital, reports with his collaborators Constance Scharff and Fernando Nottebohm of Rockefeller University and others that they have coaxed high-level neurons in adult zebra finches to be replaced by the bird's endogenous precursor cells.
"This is, we believe, the first example where it has been demonstrated that one can induce the birth of new neurons and that they actually contribute to a complex behavior," says Macklis, associate professor of neurology (neuroscience) at Harvard Medical School. "It is a step toward attempting the same in mammals," he adds.
The study plays on one of the brain's more amazing feats: every fall, a population of song-generating neurons in the so-called high vocal center of canaries dies off and the birds fall quiet. Winter sees a wave of rebirth of the same kind -- and same number -- of neurons, and in the spring, the canaries learn their songs anew. Zebra finches lack this seasonal cycle; their brains generate a constant yet tiny trickle of new neurons.
This more limited ability resembles that of mammals, where scientists now agree that multipotent precursors line the brain's inner ventricles, but only two specific types of neurons, one in the olfactory bulb and one in the hippocampus, are known to regrow at low levels.
If zebra finches, and indeed humans, have cells that could potentially repopulate brain areas, the scientists wondered, then why do they not do so? To find out whether the answer lay in the precursors themselves or in the brain environment they encounter, they tested the notion that it is the death of certain neurons that fosters the ingrowth and differentiation of precursors.
When the researchers selectively killed one kind of song-related neuron in zebra finches, they found that these birds, too, partially lost their song. Within three months, however, the finches had more or less restored their songs, and the neurons had reappeared in numbers similar to the annual rebirth in canary brains.
That ability was restricted, however, to certain neuron types. Another song-related kind of neuron that does not normally turn over did not regrow when coaxed by previous cell death, either. Further experiments to explain this and other results are ongoing, says Macklis.
The finches' re-emerging songs not only please scientists' yearning for spring, but also represent a reproducible and quantifiable higher function. This makes the birds suitable for studying a big open question of research aimed at future repair of brain function, namely whether newly incorporated neurons can function in an existing complex circuitry and contribute to behavior.
Journal
Neuron