Whether newborn nerve cells in adult brains live or die depends on whether they can muscle their way into networks occupied by mature neurons. Neuroscientists at the Salk Institute for Biological Studies pin-pointed the molecular survival gear required for a young neuron to successfully jump into the fray and hook up with other cells.
In a study published in a forthcoming issue of Nature, researchers in the lab of Fred H. Gage, Ph.D., a professor in the Gene Expression Laboratory and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases, identify a subunit of the NMDA receptor, a protein complex that transduces signals sent by neighboring cells, as the cells' life-saving equipment that allows them to integrate into the existing brain circuitry.
The NMDA receptor is activated by the neurotransmitter glutamate, a chemical released by neurons in order to transmit information to neighboring cells. Whenever the receptor picks up a glutamate signal it is stimulated and relays the signal. But for newborn neurons that signal means something else entirely -- survival.
"When we removed the NMDA receptor, that is when cells make connections in response to glutamate in the environment, the newborn neurons withered and died at a specific stage of their maturation," explains Gage. " The NMDA receptor modulates synapse formation and determines what pattern of input activity new neurons receive, which in turn determines survival or death."
Combining mouse genetics and gene transfer techniques, Gage and a team headed by former postdoctoral fellow Ayumu Tashiro, Ph.D., injected a virus carrying a pair of molecular shears capable of deleting a gene encoding part of the NMDA receptor into the hippocampus, a brain region harboring neural stem cells that give rise to new neurons. Newly born neurons infected with virus were marked by a fluorescent dye enabling detection of neurons derived from those cells.