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What Your Neural Stem Cells Aren't Telling You

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Neural stem cells (green) in the hippocampus huddle around a neuron (purple), listening for stray signals.

Neural stem cells (green) in the hippocampus huddle around a neuron (purple), listening for stray signals.

In 2000, a team of neuroscientists put an unusual idea to the test. Stress and depression, they knew, made neurons wither and die - particularly in the hippocampus, a brain area crucial for memory. So the researchers put some stressed-out rats on an antidepressant regimen, hoping the mood boost might protect some of those hippocampal neurons. When they checked in a few weeks later, though, the team found that rats' hippocampuses hadn't just survived intact; they'd grown whole new neurons - bundles of them. But that's only the beginning of our tale.

By the time 2009 rolled around, another team of researchers was suggesting that human brains might get a similar hippocampal boost from antidepressants. The press announced the discovery with headlines like, "Antidepressants Grow New Brain Cells" - although not everyone agreed with that conclusion. Still, whether the principle applied to humans or not, a far more basic question was begging to be answered: How, exactly, does a brain tell new cells to form?

"Well, through synapses, of course," you might answer - and that'd be a very reasonable guess. After all, synapses are how most neurons talk to each other: electrochemical information is "squirted" from a tiny tendril of one neuron into the tip of a tendril on another; and cells throughout most of the brain share essentially this same mechanism for passing signals along: The signals coming out of Neuron A's synapses keep bugging Neuron B by stimulating its synapses, until finally Neuron B caves under peer pressure and bugs Neuron C with the signal... and so on.

There are, however, two significant exceptions to this system.

The first exception was discovered a few years ago, as scientists got more and more curious about the role of neuroglia (also known as just "glia"), synapse-less cells that many had assumed were just there to serve as structural support for neurons. A 2008 study showed that glia help control cerebral blood flow, and research in 2010 demonstrated that some glia - cells known as astrocytes - actively listen for and respond to certain neurotransmitter messages. These so-called "quiet cells" are actually pretty loud talkers once you learn to tune in to their chatter.

The second exception to the synapse rule is even more mysterious - in large part because it's a brand-new discovery: As the journal Nature reports, a team led by Hongjun Song at the Johns Hopkins University School of Medicine have found that neural stem cells "listen in" on the stray chemical signals that leak from synapses.

You can imagine neural stem cells as being sort of "neural embryos" - depending on the surrounding conditions, they can develop into neurons or into glia. And here's what's strange about the way these cells communicate: They respond not to any single synaptic signal, but to the overall chemical "vibe" of their environment - to chronic feelings of stress, for instance. By way of response, they may morph into neurons or glia - or even tell the brain to crank out some all-new cells.

Neural stem cells seem to be particularly interested in the chemical GABA (gamma-aminobutyric acid) - a neurotransmitter that's known to be involved in inhibiting signals from other neurons. When scientists artificially block these stem cells' GABA receptors from receiving messages, the cells "wake up" and start replicating - but when those GABA signals are allowed to reach the receptors, the stem cells stay dormant.

"In this case," Song explains, "GABA communication keeps the brain stem cells in reserve, so if we don't need them, we don't use them up."

In short, leaky synapses aren't wasteful – as a matter of fact, they're essential to the brain's self-sculpting abilities. And this implies something pretty interesting: It isn't just individual signals that convey neural information, but whole experiences. In that respect, a brain - whether it belongs to a rat or a human - is unlike any computer on earth.

References:

Malberg JE et al. "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus." J Neurosci. 2000 Dec 15;20(24):9104-10.

Boldrini M et al. "Antidepressants increase neural progenitor cells in the human hippocampus." Neuropsychopharmacology (2009) 34, 2376–2389; doi:10.1038/npp.2009.75.

Gourine AV et al. "Astrocytes Control Breathing Through pH-Dependent Release of ATP." Science 30 July 2010: 329 (5991), 571-575.

Song H et al. "Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision." Nature 2012: 10.1038/nature11306

Image: Gerry Sun

The views expressed are those of the author and are not necessarily those of Scientific American.

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