Think back to high school biology. Remember the long, stringy neurons that make up your nervous system? You probably learned that these cells communicate by sending a chemical message across the small gap between them, called a synapse. That's still true, but new research shows that certain brain cells bypass the synapse altogether. Instead, they communicate by spraying a cloud of neurotransmitters into the spaces between cells, blanketing nearby neurons.
A team of Hungarian researchers at the University of Szeged made the discovery by examining a type of neuron called a neurogliaform cell. These cells are common in the brain's cortex, a region that plays a key role in many functions, including memory, attention, awareness, and language. Studies have shown that neurogliaform cells can inhibit the firing of other brain cells by releasing a neurotransmitter called GABA (gamma-aminobutyric acid), which typically transmits messages across synapses. But some studies have suggested that GABA can diffuse into the extracellular space as well, where it carries messages between neurons not connected via synapses. To create enough ambient GABA for this to happen, however, scientists speculated that many neurons would have to fire at once. The researchers set out to test this idea.
The output end, or axon, of a normal neuron is typically long and stringy. But when the Hungarian team used electron and light microscopes to examine brain tissue from rats and humans, they found that neurogliaform cells have bushy axons with many branches. These bushy axons are densely populated with sites where GABA can be released into the extracellular space, the team found. Elsewhere in the brain this occurs mainly at synapses, but only 11 of the 50 release sites examined in neurogliaform cells corresponded to a synapse, the researchers report today in Nature. Additional experiments confirmed that a single neurogliaform cell, when stimulated, releases enough GABA to inhibit the activity of nearby neurons not connected by synapses.
"That's a very striking finding," says Dimitri Kullmann, a neuroscientist at University College London. "Rather than a hose pointing at rose bushes, [the bushy axon is] like a sprinkler on your lawn." Previous studies have shown that neurotransmitters such as serotonin can carry messages to other cells that lack synaptic connections, Kullmann notes, but this is the first study to show that a single neuron can use GABA to communicate with other cells sans synapses.
The researchers also showed that neurogliaform cells contain receptors that can pick up even very low levels of GABA, suggesting that they are designed to communicate among themselves as well as with other types of cells. These same receptors are also sensitive to neurosteroids, molecules synthesized in the brain that are linked to anxiety and depression. Concentrations of these molecules can fluctuate with a woman's menstrual cycle or during pregnancy or periods of stress. So the authors posit that fluctuations in neurosteroid concentrations might affect the activity of these neurogliaform cells.
Clinical implications aside, the new work represents an important milestone in our understanding of the brain, says Alexey Semyanov, a neurophysiologist at the RIKEN Brain Science Institute in Japan. "Most of physiology now focuses on synaptic signaling, but extrasynaptic signaling cannot be ignored anymore," he says. "You can't explain how the brain works ... just based on synaptic communication."