The discovery of a new kind of cell shakes up neuroscience
Neuroscience is in great upheaval. The two major families of cells that
make up the brain, neurons and glial cells, secretly hid a hybrid cell,
halfway between these two categories. For as long as Neuroscience has
existed, it has been recognized that the brain works primarily thanks to
the 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 stabilize
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. This is why
neuroscientists have long suggested that astrocytes may have an active role
in synaptic transmission and participate in information processing.
However, the studies conducted to date to demonstrate this have suffered
from conflicting results and have not reached a definitive scientific
consensus yet. By identifying a new cell type with the characteristics of
an astrocyte and expressing the molecular machinery necessary for synaptic
transmission, neuroscientists from the Department of Basic Neurosciences of
the Faculty of Biology and Medicine of the University of Lausanne (UNIL)
and the Wyss Center for Bio and Neuroengineering in Geneva put an end to
years of controversy.
The Key to the Puzzle
To confirm or refute the hypothesis that astrocytes, like neurons, are able
to release neurotransmitters, researchers first scrutinized the molecular
content of astrocytes using modern molecular biology approaches. Their goal
was to find traces of the machinery necessary for the rapid secretion of
glutamate, the main neurotransmitter used by neurons. “The precision
allowed by single-cell transcriptomics approaches enabled us to demonstrate
the presence in cells with astrocytic profile of transcripts of the
vesicular proteins, VGLUT, in charge of filling neuronal vesicles specific
for glutamate release. These transcripts were found in cells from mice, and
are apparently preserved in human cells. We also identified other
specialized proteins in these cells, which are essential for the function
of glutamatergic vesicles and their capacity to communicate rapidly with
other cells,” says Ludovic Telley, Assistant professor at UNIL, co-director
of the study.
New Functional Cells
Next, neuroscientists tried to find out if these hybrid cells were
functional, that is, able to actually release glutamate with a speed
comparable to that of synaptic transmission. To do this, the research team
used an advanced imaging technique that could visualize glutamate released
by vesicles in brain tissues and in living mice. “We have identified a
subgroup of astrocytes responding to selective stimulations with rapid
glutamate release, which occurred in spatially delimited areas of these
cells reminiscent of synapses,” says Andrea Volterra, honorary professor at
UNIL and visiting faculty at the Wyss Center, co-director of the study.
In addition, this glutamate release exerts an influence on synaptic
transmission and regulates neuronal circuits. The research team was able to
demonstrate this by suppressing the expression of VGLUT by the hybrid
cells. “They are cells that modulate neuronal activity, they control the
level of communication and excitation of the neurons,” says Roberta de
Ceglia, first author of the study and senior researcher at UNIL. And
without this functional machinery, the study shows that long-term
potentiation, a neural process involved in the mechanisms of memorization,
is impaired and that the memory of mice is impacted.
Links With Brain Pathologies
The implications of this discovery extend to brain disorders. By
specifically disrupting glutamatergic astrocytes, the research team
demonstrated effects on memory consolidation, but also observed links with
pathologies such as epilepsy, whose seizures were exacerbated. Finally, the
study shows that glutamatergic astrocytes also have a role in the
regulation of brain circuits involved in movement control and could offer
therapeutic targets for Parkinson’s disease.
“In between neurons and astrocytes, we now have a new kind of cell at hand.
Its discovery opens up immense research prospects. Our next studies will
explore the potential protective role of this type of cell against memory
impairment in Alzheimer’s disease, as well as its role in other regions and
pathologies than those explored here,” projects Andrea Volterra.
Specialized astrocytes mediate glutamatergic gliotransmission in the CNS
Nature. 06 September 2023
https://www.nature.com/articles/s41586-023-06502-w
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