The discovery of a new kind of cell revolutionizes neuroscience

The identification of the molecular machinery required for the rapid release of
The identification of the molecular machinery required for the rapid release of neurotransmitters has led to the discovery of a new type of functional cell in the brain. The newly discovered cells have the characteristics and shape of astrocytes - different subtypes are visualized here by immunohistochemistry in the hippocampus - but function more like neurons with the ability to release the neurotransmitter glutamate Telley/Volterra, Unil
A research team from the University of Lausanne and the Wyss Center has discovered a new type of cell essential to brain function. Hybrid in composition and function between the two hitherto known types of brain cells - neurons and glial cells - these cells of a new order are found in several brain regions from mice to humans. The study, published in the journal Nature, shows that they facilitate memorization and movement control, and counteract the onset of epileptic seizures.

Neuroscience is undergoing a major upheaval. The two main families of cells that make up the brain - neurons and glial cells - were secretly hiding a hybrid cell, halfway between these two categories. It is well known that the brain functions essentially thanks to neurons and their ability to rapidly elaborate and transmit information through their networks. To support them in this task, glial cells perform a series of structural, energetic and immune functions, as well as stabilizing physiological constants. Some of these glial cells, known as astrocytes, intimately surround synapses, the points of contact where neurotransmitters are released to transmit information between neurons. For this reason, neuroscientists have long suggested that astrocytes may play an active role in synaptic transmission and information integration. However, studies carried out to date to demonstrate this have suffered from contradictory results and have yet to reach a definitive scientific consensus. By identifying a new cell type with the characteristics of an astrocyte and expressing the molecular machinery required for synaptic transmission, neuroscientists from the Department of Basic Neuroscience in the Faculty of Biology and Medicine at the University of Lausanne (UNIL) and the Wyss Center for Bio and Neuroengineering in Geneva have put an end to years of controversy.

The key to the puzzle

To confirm or refute the hypothesis that astrocytes, like neurons, are capable of releasing neurotransmitters, the researchers first examined the molecular content of astrocytes using modern molecular biology approaches. Their aim was to find traces of the machinery required for the rapid secretion of glutamate, the main neurotransmitter used by neurons. Thanks to the precision of single-cell transcriptomics techniques, we were able to identify transcripts of VGLUT proteins, responsible for filling neuronal vesicles to release glutamate, in cells with an astrocyte profile. This observation is valid in both mice and humans. Moreover, we detected in these same cells other proteins crucial to the function of glutamatergic vesicles", explains Ludovic Telley, assistant professor at the University of Lausanne and co-director of the study.

New functional cells

Next, the neuroscientists investigated whether these hybrid cells were functional, i.e. capable of releasing glutamate at a rate comparable to that of synaptic transmission. To do this, the research team used an advanced imaging technique capable of visualizing the glutamate released by the vesicles in tissues of brain origin and in living mice. We have identified a subgroup of astrocytes that respond to selective stimulation by rapidly releasing glutamate from spatially delimited areas of these cells reminiscent of synapses", says Andrea Volterra, Honorary Professor at the University of Lausanne, Visiting Faculty at the Wyss Center and co-director of the study.

Moreover, this release of glutamate influences synaptic transmission and controls neuronal circuits. The research team succeeded in demonstrating this by suppressing VGLUT expression by these hybrid cells. These are cells that modulate neuronal activity, controlling the level of communication and excitation of neurons", explains Roberta de Ceglia, researcher at the University of Lausanne and first author of the study. And without this functional machinery, the study shows that long-term potentiation, a neuronal process involved in the mechanisms of memorization, is impaired and that the mice’s memory is impacted.

Links with brain pathologies

The implications of this discovery extend to brain disorders. By specifically disrupting glutamatergic astrocytes, the research team was able to demonstrate effects not only on memory consolidation, but also on pathologies such as epilepsy, whose seizures were exacerbated. Finally, the study shows that glutamatergic astrocytes also play a role in regulating brain circuits involved in movement control, and could offer therapeutic targets for Parkinson’s disease.

Between neurons and astrocytes, we now have a new kind of cell on hand. They open up immense research prospects. Our next studies will explore its potential protective role against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here’, Andrea Volterra projects.