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Colorized image with brain cells highlighted in different colours: neurons (green), astrocytes (red), glia cells (blue). Credit: selvanegra/ iStockphoto/ Getty Images.

Scientists have known for decades that the nervous system comprises two families of cells: glial cells and neurons. Neurons process and transmit information through their networks via connections called synapses, while glial cells nestle between neurons providing structural and physiological support.

A team that includes researchers from the IRCCS Santa Lucia, and the University of Rome Tor Vergata has found a group of astrocytes, which are a subset of glial cells, that plays a role in synaptic transmission and is involved in information processing1. These cells have characteristics that were never before observed in the astrocyte family, placing them halfway between glial and neuronal cells. Specifically, researchers found that they can release the neurotransmitter glutamate at a speed that would allow a fast modulation of synaptic transmission.

"The hypothesis that astrocytes can affect neuronal functions by releasing transmitters has been advanced many years ago, but the evidence was controversial,” says Ada Ledonne, who is now at the University of Rome Tor Vergata, and previously worked at the University of Lausanne in the team of the study coordinator Andrea Volterra. “Our study provides the first direct evidence.” Part of the research related to this study was also carried out at the Fondazione Santa Lucia IRCCS, by the neurologist, Nicola Biagio Mercuri.

“We used single-cell transcriptomic and bioinformatic analyses that allow us to demonstrate that glutamatergic astrocytes are present in different brain regions in mice and are apparently preserved in humans,” Ledonne continues. These regions include the hippocampus and the dentate gyrus, that are both involved in the formation of memories, the visual cortex and the substantia nigra, that is involved in motor control. In particular, the scientists found that proteins called glutamate transporters were expressed in cells with an astrocytic profile. “These proteins fill neuronal vesicles with glutamate, thus they are key for glutamate release,” says Ledonne. The team also identified other specialized proteins in these subtypes of astrocytes that are essential for the release of glutamate outside the cell.

By looking at their interaction with neurons, the researchers were able to prove that these glutamatergic astrocytes influence the transmission of information between neurons and synaptic plasticity in brain circuits involved in memory processing and movement control.

"Just like high-definition photography makes previously overlooked details clear, the techniques used in this study led to the identification of one specific astrocyte subgroup capable of fast glutamate release,” says Stefano Taverna, a neurophysiologist at San Raffaele Hospital in Milan who was not involved in the study. “Since glial cells are involved in several neurological disorders, including Alzheimer's and Parkinson’s diseases, these findings may bring advances in targeted therapeutical treatment that could correct malfunctions on a subset of cells, while leaving others unaffected."