In the middle of a pitch-black room, a very special mouse lies motionless on a microscope stage. Months before, the mouse had two small holes cut out of its skull, revealing the dura–the brain’s outer membrane–and the blood vessels below. The holes have been permanently covered with clear glass so that scientists can peer directly into the mouse’s brain, where some of its neurons glow green under the laser light of a microscope.
For images of this brain-watching lab, click here.
As the anesthetized mouse sleeps, Wei-Chung Lee, a postdoc at MIT’s Picower Center for Learning and Memory, snaps a series of pictures of a single neuron. He will combine these photos into a 3-D image of the neuron and compare it with an image of the same cell created a week ago, to determine how it has changed over time.
The technique has given MIT scientists an unprecedented look at the surprising growth of neurons in the course of an adult mouse’s everyday life. “You see the full range of types of growth you see during development, such as growth spurts, extensions, retractions, or new additions,” says Elly Nedivi, the associate professor of neurobiology at MIT who heads the research. “This is what the brain is doing on a day-to-day basis.” Nedivi helped develop the new imaging procedure in collaboration with Peter So, an imaging expert in MIT’s bioengineering department, hoping to better explore changes in complex webs of branchlike projections that relay messages between neurons. What she has found is helping change the scientific picture of the brain.
Once upon a time, scientists thought that the adult brain was mostly static in structure–that after the neural growth spurts of infancy and adolescence, connections between neurons were permanently laid out, like a network of paved roads. But a growing body of evidence suggests that the adult brain has a surprising capacity to reorganize. Nedivi and her team have provided new support for this idea, furnishing the first proof in living animals that neurons’ information-exchanging projections can grow and retract in adulthood, in ways that are qualitatively similar to what they do early in life.
Neuroscientists knew that some neural changes must take place in the adult brain, because we continue to learn throughout life. “But people didn’t know if that plasticity was accompanied by structural changes,” says David Kleinfeld, a neuroscientist at the University of California, San Diego. Nedivi and her collaborators, he says, have shown that neurons of at least one particular type “continue to grow and evolve in the adult mouse.”
The key to Nedivi’s discovery was the ability to look at the same neuron in a living animal week after week. Most previous research on neuroplasticity–the brain’s ability to form new neural connections–examined brain slices, sections of brain that are kept alive for a short time. Although such in vitro studies allow scientists to test how neural connections are affected by specific factors, such as jolts of electricity or different types of drugs, they can’t show what happens to neurons in the living brain as an animal grows old, or develops a disease, or is raised in isolation.
Looking at the same cell for a period of weeks can reveal the slow growth of neurons in the brain. Nedivi hopes to use the process to determine what goes awry in the brains of mice engineered to model Alzheimer’s and schizophrenia. Such studies will offer both new information about the human diseases and a way to test novel therapies.
The researchers also hope to determine the best ways to encourage brain cells to grow. If neurons could be coaxed to grow new projections in specific parts of the brain or spinal cord, they might be able to compensate for the damage caused by spinal-cord injury or stroke.