A gamma wave is a rapid, electrical oscillation in the brain. A scan of the academic literature shows that gamma waves may be involved with learning memory and attention—and, when perturbed, may play a part in schizophrenia, epilepsy Alzheimer's, autism and ADHD. Quite a list and one of the reasons that these brainwaves, cycling at 25 to 80 times per second, persist as an object of fascination to neuroscientists.
Despite lingering interest, much remains elusive when trying to figure out how gamma waves are produced by specific molecules within neurons—and what the oscillations do to facilitate communication along the brains' trillions and trillions of connections. A group of researchers at the Salk Institute in La Jolla, California has looked beyond the preeminent brain cell—the neuron— to achieve new insights about gamma waves.
At one time, neuroscience textbooks depicted astrocytes as a kind of pit crew for neurons, providing metabolic support and other functions for the brain's rapid-firing information-processing components. In recent years, that picture has changed as new studies have found that astrocytes, like neurons, also have an alternate identity as information processors. This research demonstrates astrocytes' ability to spritz chemicals known as neurotransmitters that communicate with other brain cells. Given that both neurons and astrocytes perform some of the same functions, it has been difficult to tease out what specifically astrocytes are up to. Hard evidence for what these nominal cellular support players might contribute in forming memories or focusing attention has been lacking.
The collaboration at Salk—with contributions there from the laboratories of Terrence Sejnowski, Inder Verma and Stephen Heinemann—began by doing experiments that showed that a rise in calcium within astrocytes preceded the onset of gamma waves in slices of tissues from the hippocampus, a structure in the brain involved in memory formation. The researchers then went on to seek firmer proof that astrocytes play a pivotal role in generating the gamma waves.
They engineered into mice a genetic switch that could turn off—and then reactivate—the release of neurotransmitters from the astrocyte. The neurotransmitter is discharged after levels of calcium within the cell have risen to a certain level. Hindering release of the neurotransmitter glutamate prevented astrocytes from communicating with nearby cells. The shutdown weakened the gamma waves in the brain of a living mouse. The ability of the researchers to flip the switch and observe the change in oscillations suggests a strong cause-and-effect relationship between astrocytes' signaling and the resulting strength of the gamma waves. The work was published in a recent edition of the Proceedings of the National Academy of Sciences.
"Oscillations in brain waves are important in coupling the firing of groups of neurons together into functional assemblies. This is critical for information processing" comments, in an e-mail, R. Douglas Fields, a researcher at the National Institutes of Health, and an expert on glia, the class of brain cells other than neurons, which includes astrocytes. "Previously, rapid oscillations in neuronal firing were understood to arise from neuronal networks driving other neurons in synchrony, and that is still true, but this new work extends beyond neurons to show that glial cells called astrocytes release neurotransmitters that promote fast oscillations in groups of neurons and thus the coupling of nerve cells into functional groups."
The weakening of gamma waves when the astrocyte signaling was suspended did not make the mice keel over and lose consciousness. But a cognitive test showed that they did not, as expected, spend a lot of time getting to know and learn about a new object. This aberrant behavior reversed when the genetic switch turned the astrocyte signaling back on. "By finding a way to selectively block gamma we have shown the necessity of these oscillations for novel object recognition," Sejnowski says. "This is the first strong evidence for a causal link. But it is still just the first step. Many more tests are needed." (Sejnowski explains more in a video.)
A mouse endowed with an astrocyte signalling switch may prove useful in future experiments—and may enable the researchers to continue to explore how gamma waves enable recognition of what's new and different, a cognitive task equally essential for humans to make their way in the world.
Image Source: Togo Picture Gallery/Wikimedia Commons