'For some people, research can be such a turnoff if things don't go well with experiments. That things went so well here has spurred me on to do more research in neuroscience,' says Matthew Kayser, whose research in Mark Bear's lab yielded a recent paper in Science
Matthew Kayser '00 came to Brown four years ago expecting to study pre-med. But in his first semester, he fell in love ... with neuroscience.
"Without question, I discovered that neuroscience is where my passion lies," said Kayser.
Captivated by Professor Mark Bear in Neuroscience 1, Kayser eventually joined Bear's lab, spending four semesters and two summers studying the mechanism of protein synthesis around nerve cells.
For Kayser, hooking up with Bear, a Howard Hughes Medical Institute investigator, was the right move at the right time. The team of Kayser, Bear and postdoctoral researcher Kim Huber, the study leader, produced a string of data to suggest a novel mechanism existed behind the decrease in strength of synapses in the brain. Synaptic weakening is thought to be a key process in memory creation and storage. Synapses are the connections between neurons, or nerve cells.
Kayser's work on the project comprised his honors thesis. The bulk of that thesis appeared in an article in the prestigious journal Science on May 18.
The article described the machinery at the synapse for the synthesis of new proteins that depress synaptic strength. Although synapses have the machinery to make proteins, there was no evidence that this machinery can function to change synapses, Kayser said.
The study is the first "demonstration in mammals that when synapses change, the modification depends on new proteins created specifically at the site," said Huber. This synaptic chemical activity is an efficient way for the brain to make new proteins and change existing ones rapidly, she said. "The mechanism appears to be a viable way for the brain to express its changes. We think this activity also may be a way that the structure, or shape, of synapses can be altered."
The increase or decrease in strength among synapses and the subsequent changes in memory are based on sensory-driven experiences. Synaptic strengthening or weakening also occurs during the brain's development. The findings hint that connections in the brain can be modified on an individual basis, facilitating long-term memory storage.
"It is important to understand the mechanism by which connections are weakened, not only because such understanding may yield insight into long-term memory, but also because this is a fundamental part of normal brain development," Bear said.
The study was conducted in rats. The researchers worked with tissue from the hippocampus region of the brain, separating synapses from their cell bodies. Even after the cells and synapses were cut apart, the synapses continued to be modified by local protein activity, indicating that synaptically synthesized proteins are involved.
This led the researchers to introduce specific inhibitors of the protein synthetic machinery directly to the synapses. The synaptic depression was blocked, providing further evidence that the proteins are made at the synapse. Follow-up experiments, in which the activation of genes at the cell body was blocked, reinforced that the new proteins are synthesized directly at the synapses.
The Bear lab is continuing the research, studying what types of proteins are being made at the synapses and how experience rapidly regulates synapses through local protein synthesis.
Kayser hopes to spend the next year as a science writer or general reporter. He plans to enter an M.D./Ph.D. program in fall 2001. Kayser wants to learn what physicians learn, but his goal is to continue studying the brain.
"For some people, research can be such a turnoff if things don't go well with experiments," he said. "That things went so well here has spurred me on to do more research in neuroscience."