Researchers Used Multiphoton Microscopy to Measure Protein Translation

Scientists at the University of Pennsylvania School of Medicine have discovered a pattern to protein manufacture in the hippocampus, the part of the brain devoted to making memories.

Christy Job, PhD, a postdoctoral neurobiologist with James H. Eberwine, PhD, Professor of Pharmacology at Penn, measured a protein as it was being made in structures of brain cells called dendrites. "The patterns of electrical stimulation which make memories are well-established, but how those memories are stored is still unexplained," said Job. "We decided to tackle this from a completely different angle by looking at protein synthesis in dendrites."

Job and Eberwine grew particular cells from the hippocampus called neurons that extend long structures (dendrites) away from the main portion of the cell, known as the cell body. Cell bodies store the genetic code (the DNA) so a message, mRNA, which is made from the DNA, moves from the cell body to dendrites.
Using a procedure known as multiphoton microscopy, Job and Eberwine were able to measure translation of this message into a protein that fluoresces. Multiphoton microscopy enabled them to examine the pattern of fluorescence across space and time.

"We thought that the rate of translation might be different in dendrites, but not only was it exponentially faster than translation in the cell body, it was also faster at particular places in each dendrite," Eberwine said.

The research, which will be published in the journal Proceedings of the National Academy of Science on October 23, could have important implications for other research into how memories are stored in the brain. Neuronal dendrites are known to pick up and convey information in the form of electrical pulses, but they could also store information by synthesizing proteins from mRNA templates.

"This raises the possibility that there is a pattern or code in the order of translation and mechanics of the translational process that exists in these translation sites at the dendritic level for the formation of memories," Eberwine said. "It could also be important for illnesses involving memory loss or mental retardation, such as Alzheimers and fragile X retardation."

The study was funded by the National Institutes of Health.


Editor's note: Eberwine may be reached directly at: 215-898-0420.


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