A 36-year-old man named Santiago Ramón y Cajal set up a home laboratory in his Barcelona home in 1888 and began examining under his microscope sections of human brains obtained from the numerous corpses at the neighboring Hospital de la Santa Cruz. Cajal encountered an “inextricable forest” on the other side of the lens, but he entered this jungle and showed that the brain is organized into individual cells, with neurons being the main actors of thought. Italian neuroscientist Andrea Volterra has been telling his students at the University of Lausanne (Switzerland) the story of Cajal for years, but this Wednesday he announced the discovery of “a new cell type” in the human brain.
The density of this brain jungle is unimaginable. The 1.5-pound gray organ in the human skull is made up of about 86 billion neurons with trillions of communication points between them. Until Cajal emerged, the scientific community believed that the brain was a diffuse collection of cells physically connected to one another. The Spanish researcher showed that they were independent entities, although they did caress and communicate with what he poetically called “kisses,” now known by a more boring term: synapses.
Neurons are surrounded by another family of cells called glial cells, which act as supports. Glia means glue in Greek. It is the glue of ideas. One of these cells is the astrocyte, named for its star shape. A single astrocyte can participate in two million kisses between neurons. In these kisses, neurons send messages containing chemicals, specifically glutamate, a molecule made up of five carbon atoms, nine hydrogen atoms, one nitrogen atom, and four oxygen atoms (C5H9NO4). This process is essential to human abstract thinking.
Volterra’s team has discovered a new cell type that doesn’t belong to the canonical categories of neuron or astrocyte. According to the Italian, these are “hybrid cells”. Neuroscientist Liset Menéndez de la Prida believes it is a “transcendental discovery” that will change our understanding of how the brain works and how it malfunctions.
Volterra called this new cell type “glutamatergic astrocytes”. According to Menéndez de la Prida of the Cajal Institute in Madrid, it is a subpopulation of astrocytes that are part of the molecular machinery of neurons to release glutamate. “Information between neurons is fast, on the order of a few milliseconds to tens of milliseconds when it occurs between multiple neurons in a chain (polysynapses). In contrast, astrocytes can take several seconds to transmit information. “This subpopulation showed sub-second responses, which is close to the magnitude of polysynaptic responses,” recalls Menéndez de la Prida, who did not take part in the research. The neuroscientist emphasizes that it is a small cell population and that its true proportion in the brain is unknown, but emphasizes that it is “a very groundbreaking result”.
Andrea Volterra believes her discovery “shakes the foundations of neuroscience” because it challenges current knowledge of how the brain works and how its disorders arise. Their study, published Wednesday in the journal Nature, shows that glutamatergic astrocytes are concentrated in brain regions involved in memory. One of these, the hippocampus, is one of the most unstable areas at the onset of Alzheimer’s disease. “We therefore have reasonable grounds to suspect that our cells could be involved,” explains Volterra.
The team also observed that glutamatergic astrocytes play a role in a circuit that controls movement and is altered in Parkinson’s disease: the nigrostriatal dopamine pathway. “We have not yet examined the distribution of these cells in other brain regions. What we findl guide our future investigations. For example, if we find high concentrations of these cells in the prefrontal cortex (the area of the brain behind the forehead), we will immediately study their role in decision-making and how they change in schizophrenia,” explains Volterra. “When we find them in the horns of the spinal cord, we think of amyotrophic lateral sclerosis.”
Neuroscientist Marta Navarrete welcomes the new study but believes glutamatergic astrocytes are a subtype of astrocytes rather than a new cell type. “Astrocytes have been known since the time of Cajal. These cells were always thought to nourish neurons and provide their structural support, but they are now revealed to be far more important. They intervene in the memory and learning process, in fear, in all the superior emotions that a human being can have,” emphasizes Navarrete, also from the Cajal Institute. Volterra’s work suggests the existence of nine classes of astrocytes, which would lead to more than a hundred types of neurons.
The researcher who first observed that astrocytes are involved in higher information processes was another Spaniard, Alfonso Araque, currently at the University of Minnesota (USA). In 1999, Araque abandoned the subject of the kiss between two neurons and postulated the concept of the “triple synapse,,” in which astrocytes also play a fundamental role. Navarrete, a student of Araque, recalls that there is still resistance to this approach. “The idea that there are types of astrocytes that are specialized for certain functions is not accepted in the scientific community. It is not fully accepted that there may be more cells (besides neurons) that are heavily involved in information processing,” he laments. Andrea Volterra’s team’s new discovery adds even more complexity to the unimaginable human brain.
