New findings are challenging the current understanding of how non-neural brain cells contribute to brain signaling, by showing that calcium levels in these cells do not affect synaptic activity.

An astrocyte Image: Wikimedia commons, Dantecat

The results appear in this week's Science.

In the past couple of years, the idea that these non-neural brain cells, known as glial cells, participate in neurotransmission "had been widely accepted," Frank Kirchhoff, a cellular and molecular neurobiologist at the Max Planck Institute for Experimental Medicine, who did not participate in the research, wrote in an email to The Scientist. "Therefore, the scientific community was rather surprised to see" that calcium levels in glial cells have no affect on neurotransmission in the hippocampus, added Kirchhoff.

For decades, scientists believed that astrocytes -- the major glial cells of the central nervous system -- only served nutritional and structural support to neurons. But over the past ten years, evidence has surfaced suggesting that astrocytes play a more active role in synaptic communication, with increases in intracellular calcium levels in astrocytes triggering the release of gliotransmitters -- chemicals from astrocytes which regulate synaptic transmission.

The new results throw yet another curveball to the field. By creating two genetically modified mouse lines, Cendra Agulhon, a neurobiologist at University of North Carolina at Chapel Hill, and her colleagues manipulated calcium signaling in astrocytes. Mice in which calcium signaling was blocked showed similar neurotransmission and synaptic plasticity to mice with elevated calcium levels, suggesting that astrocytic calcium had no effect on neural activity.

Agulhon said she was surprised by the findings and believes that the difference from previous results is largely a result of the methodology. Compared to the pharmacological approaches used in previous studies, studying genetically modified mice represents a "more physiological" way to examine gliotransmission, she said. Pharmacological methods, however, can produce gliotransmission simply as an experimental artifact, she said.

However, the techniques used in this study measure calcium levels at too large a scale that may miss interactions between neurons and astrocytes that occur at finer resolution, said Kirchhoff, who authored an opinion in the same issue of Science. "We still miss a comprehensive understanding how these cells interact at the molecular level with their neuronal neighbourhood."

Novel approaches to studying gliotrasmission will be required to fully understand the process, Kirchhoff added. Studying behavioral changes before and after genetic mutation, for example, or creating better imaging techniques to record calcium signals from astrocyte processes, will help scientists better understand how these non-neural brain cells participate in neuronal signaling, he said.

"We are still at very early stages in understanding the role of astrocytes," Agulhon agreed. "We are developing genetic tools to investigate the role of these astrocytes in physiology, but also in neurophysiological diseases."


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