"We know that we're knocking out a gene that's only expressed in this one cell population, of glia," Melom says. "It's unambiguous that the seizure originally arises from defects in the glia rather than in the neurons."
Littleton's lab uses fruit flies as a model organism for studies of neuronal development and the formation of synapses, the connections between neurons. To pinpoint the genes involved in these processes, they mutate fruit fly genomes and screen the resulting flies for abnormal traits. Most of the mutations occur in neurons, but in this case, the researchers found that flies with glial mutations in a gene they named zydeco caused the flies to undergo seizures at high temperatures.
Further study of the zydeco gene revealed that its normal function is to get rid of calcium inside the glia. This helps to regulate glial fluctuations in calcium levels, which the MIT team observed for the first time in fly glia.
When zydeco is mutated, the fluctuations stop, causing calcium to build up inside the glial cells. Through an unknown process, this induces nearby neurons to become hyperactive and makes them more likely to seize in response to heat, cold or shaking. "It's clear that their nervous systems are hyperexcitable to a lot of environmental stimuli," Littleton says.
This is one of the few examples scientists have found of glia activity influencing neurons' firing.
"Neurons are still carrying the main information," Littleton says. "They're the ones talking. But glia are somehow listening in and modulating the neurons' output. If that output is disrupted by glia, it causes the whole system to fail."
Sources of excitation
|Contact: Sarah McDonnell|
Massachusetts Institute of Technology