Live wires: axons can influence nerve impulses.

The "wires" that carry electrical signals among nerve cells in the brain can influence the threshold at which the cells will send those signals, research on mouse-brain tissue shows.

The finding challenges the conventional view of nerve cells, or neurons. In that scenario, processes within a nerve cell determine whether or not to fire an electrical impulse, and the wire, called an axon, is a passive carrier of that signal.

"[Our research] says that the dogma is incorrect," says lead scientist Raju Metherate of the University of California, Irvine. A more active role for axons could be important for understanding how the brain processes sensory information. It could also have implications for the understanding of neurological diseases such as schizophrenia, Metherate says.

The scientists exposed the axons of isolated mouse neurons to nicotine, which mimics a natural chemical messenger in the brain called acetylcholine. Previous research had shown that axons in several regions of both mouse and human brains have receptors for acetylcholine, but the function of those receptors wasn't dear. Without nicotine, a weak input signal triggered the neurons to fire only 35 percent of the time. With axons exposed to nicotine, neurons in the tissue samples fired twice as often in response to the same signal. The change indicated that nicotine was lowering the neurons' thresholds, the researchers report in the September Nature Neuroscience.

"We believe this [influence by axons] is a major reason that nicotine enhances cognitive functioning," Metherate says. The neurons that Metherate's team studied connect a region in the center of the brain called the thalamus--which acts as grand central station for incoming sensory signals--and the brain's cortex, where thought occurs. So, lowering the firing threshold of these neurons would increase the amount of sensory stimulation reaching the cortex.

"I'm enthused by this research," comments Marina Picciotto, a psychiatrist- and nicotine expert at Yale University. "It's only now that work on nicotinic receptors [on axons] is showing the role they play in modulating sensory input." Poor communication between the thalamus and cortex could contribute to disorders such as schizophrenia, some scientists hypothesize. If so, the new research could help explain why roughly 90 percent of people with schizophrenia smoke. "It may be that they're doing it to self-medicate," Picciotto says.

The mechanism by which acetylcholine receptors on axons lower neurons' firing thresholds remains uncertain, Metherate says. However, receptors located close to the base of an axon--which is where it meets the cell body and where nerve impulses originate-had a larger influence on the threshold than did receptors farther away.

The researchers didn't look at neurons in other brain regions. Scientists know, however, that at least some neurons, such as those making up the thick band that connects the brain's left and right hemispheres, don't have acetylcholine receptors on their axons. It remains unknown whether or not axons carry receptors for other chemical messengers, such as dopamine and serotonin.