Synapses between nerve cells in the brain undergo constant remodeling, which is the basis of learning. An LMU team has now traced the molecules that direct remodeling and shown that they circulate in the living cell like running sushi.
The human brain is like a long-term construction site—there’s always something else to be done. This is certainly true of synapses, the functional links between nerve cells, which are constantly being strengthened, attenuated or demolished. Indeed, this process termed synaptic plasticity is the basis of our ability to store and recall information—in other words, to learn. The instructions for the synthesis of necessary components, which are encoded in molecules known as messenger RNAs (mRNAs), are delivered to the specific synapses that need them by a specialized transport system. But how the blueprints reach their destinations is poorly understood. In order to learn more about the underlying mechanisms, cell biologist Professor Michael Kiebler and his group at the LMU Biomedical Center have now followed the transport of individual mRNAs to specific synapses. Their analysis shows that the same mRNA can be presented to potential addresses several times—a system which the researchers compare to running sushi, the use of an ‘endless’ conveyor belt to enable patrons to pick and choose from the delicacies on offer.
In order to serve the extensive network of synapses on a typically elongated process termed dendrite, the mRNAs must be transported from the nucleus in the cell body to the terminal branches at the end of the process. To monitor this process, the LMU team used cell cultures derived from neurons isolated from the hippocampus of the rat, which serves as a model for the human hippocampus. “We labelled specific mRNAs in living cells with a fluorescent dye, which enabled us to track their progress in real time,” Kiebler explains. “This approach permitted us to determine, for the first time, whether or not a given molecule is delivered directly to a particular synapse, and whether different mRNAs are handled differently in this respect. In one case, we were able to follow how an mRNA entered one of the spine-like processes extended by a dendrite,” he says. “Dendrites act as antennas that receive inputs from synapses on other cells.” The observations revealed that one and the same mRNA may repeatedly circulate back and forth between the cell body and the nerve processes—like sushi wending its way between the tables in a restaurant—until it finds a synapse that needs it.
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