Structure Essential for Brain Remodeling Identified
DURHAM, N.C. -- During learning and memory formation, the brain builds or remodels tiny structures on the surface of its nerve cells to store the new information. Now, a team led by Duke University Medical Center researchers has discovered where the brain gets the raw materials for such construction -- and has even taken "home movies" of the process.
The discovery, made in rodents, may lead to advances in understanding Alzheimer's disease, autism and age-related memory loss, and could point to potential treatments for these and other neurological conditions, said senior study investigator Michael Ehlers, M.D., Ph.D., an associate professor of neurobiology and a Howard Hughes Medical Institute investigator at Duke.
The researchers published the findings in the Dec. 7, 2006, issue of the journal Neuron.
The research was funded by the National Institutes of Health, the American Health Assistance Foundation and the Raymond and Beverley Sackler Foundation.
The team focused on specific structures in brain nerve cells, or neurons, called dendritic spines. These are tiny bumps that form on the surface of dendrites, which extend off neurons like tree branches and receive chemical signals from other neurons. Each dendritic spine "talks" with its counterpart on a nearby neuron, and collectively the two structures comprise the "synapse" that links the neurons.
The brain stores new information by changing the structure of the synapses, Ehlers said. "If we need to remember a name, directions to a location or how to perform certain motor tasks -- anything involving learning or memory, really -- our brain does it by changing the properties of synapses," he said.
During learning, synapses change in ways that make it easier for connected neurons to communicate with each other. This "plasticity" can occur in two ways. One way is structural, in which a synapse changes in size or shape; the other way is functional, in which connections between the synapses are strengthened by increasing the chemical signals sent or received by connected neurons.
In previous studies, Ehlers and colleagues at Duke found that certain cellular structures called recycling endosomes, which recycle used proteins within the cell, play an important role in controlling the functional type of plasticity. In the current study, the researchers sought to determine if recycling endosomes are involved in the structural type of plasticity as well.
To create a study model, the researchers transplanted neurons from rats into cell culture dishes. They then stimulated the neurons with chemicals and examined the cultures using a technique called live-cell imaging, in which a camera attached to a powerful microscope recorded the dendritic spines as they grew. This technique, Ehlers said, enabled the team to glimpse inside the internal world of the neuron to see how the recycling endosomes responded when neurons were stimulated.
When the scientists triggered the neurons, they saw the recycling endosomes, labeled with a green dye, streaming up and down the neurons, dipping in and out of the dendritic spines. Inside the dendritic spines, the recycling endosomes deposited pieces of recycled proteins that grew new spines or changed the shape and size of existing spines, Ehlers said.
The finding supported the team's theory that recycling endosomes transport the cargo that dendritic spines need to grow, Ehlers said.
Ehlers added that by providing a better understanding of how cells develop new synapses or strengthen existing synapses, the study may give researchers new ideas for developing drugs that target these critical cellular processes. A variety of neurological disorders, including Alzheimer's disease, autism and early forms of age-related memory loss, are characterized by the loss of synapses or by the abnormal structural development of dendritic spines, he said.
Other researchers participating in the study were Mikyoung Park, Thomas Helton and Camenzind Robinson of Duke, Jennifer Salgado and Linnaea Ostroff of the Medical College of Georgia, and Kristen Harris of the University of Texas at Austin.