Bisexual fruit flies show new role for neurochemical

Everything from the ability to concentrate, perceive and learn to debilitating illnesses such as amyotrophic lateral sclerosis, muscular dystrophy, post-traumatic stress syndrome and schizophrenia is influenced by the number of receptors on nerve cells. The more receptors each cell has at its communication points, or synapses, the better that messages are carried through the brain.

A UIC research team led by David Featherstone, assistant professor of biological sciences, has discovered that receptor numbers are controlled by the brain's level of glutamate. But it is not the same glutamate that most neuroscientists think about — the neurotransmitter that moves in message packets across the synapse. Instead, it is what Featherstone calls ambient extracellular glutamate, which just floats around the nervous system and has generally been ignored because no one knew where it came from or what it was doing.

For years, scientists failed to identify glutamate as a key neurotransmitter precisely because there was so much of it.

“It made no sense,” said Featherstone. “People figured you couldn't use glutamate to send messages because there was too much glutamate background noise in the brain. It turns out that this background noise plays an important part in regulating information transfer.”

Featherstone and his lab team found that glia cells are the source of the excess ambient glutamate. Along with neurons, these poorly understood “support” cells fill the brain.

The team discovered proteins in fruit fly glia cells that regulate the amount of ambient glutamate in the brain. Called xCT transporter proteins, they pump glutamate out of glia cells.

“When we mutate the protein, we get less ambient extracellular glutamate, more glutamate receptors, and so a stronger transfer of messages at synapses,” Featherstone said.

The gene mutation also made the flies bisexual, leading him to name the gene “genderblind.”

“The mutants are completely bisexual, but fertile. It's the first gene that really specifically affects homosexual behavior without affecting heterosexual behavior,” he said.

“Trying to understand fly bisexuality sounds silly, but these behavioral changes are important evidence that ambient extracellular glutamate and xCT transport proteins play important, unsuspected roles in brain function,” Featherstone said. “We think we'll be able to learn a lot about perception and development from figuring out exactly what's happening in these flies.

“It's amazing how many biomedical breakthroughs have come from crazy directions.”