The banner shows four astrocytes reconstructed from segmentation of a 3DEM stack, in the background

New Research Topic in Frontiers in Neuroanatomy explores an ultrastructural insight of astrocytes at a microscale level.

— By Laura E Perlini, PhD, Journal Development Specialist Frontiers in Neuroanatomy

For many years, glial cells have been considered less appealing than their neuron fellows and thought to be simple insulators for neuronal communication. Being glia viewed just as “cellular glue”, the interest of the scientists has focused mainly on neurons. Consequently, the technological advancements in brain research have largely been driven by the need of understanding neuronal cells.

Although glial scientists had to adapt existing approaches to study glial cells, years of research have proven the “glue” theory wrong, and glia are gaining increasing attention in the scientific world. Glia are active participants in brain functions and involved in several mechanisms: from neuronal survival and function to formation, plasticity, and maintenance of neural circuits.

Among glial cells, the astrocytes, “star cells”, were immediately recognized as a potential metabolic bridge between the circulatory system and neurons upon their identification. Initially, given their obvious supporting role, no further effort was put in their characterization. However, increasing evidence suggests that astrocytes are crucial to the complex functions of the human brain. For instance, humans not only have the biggest but also the most numerous astrocytic cells among all animal species and therefore, astrocytes might have played an essential role in the evolution of the human brain.

We have interviewed Dr Corrado Calì, a postdoc in the laboratory of Pierre Magistretti at KAUST, Saudi Arabia who has recently launched the Research Topic “The Glia Atlas: an Ultrastructural Insight of Astrocytes at a Microscale Level” in Frontiers in Neuroanatomy together with Drs Christel Genoud and Pierre J Magistretti. Dr Calì studies astrocytes and investigates the cellular and molecular mechanisms of neuroenergetics, with a focus on glycogen and lactate metabolism. He is an electronic engineer by training and became interested in neuroscience during his master internship. Following that experience, he started a Ph.D. course in Neuroscience and developed a strong interest in astrocytes and high-resolution microscopy. Indeed, Dr Calì carries on his research by means of morphological and ultrastructural analyses. He is currently developing qualitative and quantitative analysis techniques based on three-dimensional reconstructions from electron microscopy (3DEM), as well as visualization environment using virtual reality to help visual assessment of the complex 3D morphologies of astroglial cells.

Dr Calì says Astrocytes’ physiology is extremely challenging because there is still a lot to find. The topic is highly debated, and every new discovery could potentially change the textbooks. I do consider astrocytes more complex than neurons and I’m convinced that one of the keys to the complexity of astrocytes relies on their extremely convoluted, star-like morphology. Since the astrocytic morphology is at the basis of astrocyte’s activity, we must elucidate it. I strongly believe we should develop innovative strategies specifically designed to study astrocytes. That’s why I spend a lot of time in developing visual analytical tools to ease astrocytes’ exploration with virtual reality.

Why is this Research Topic so timely?

Many aspects of astrocytes physiology are under heavy debate. In many years of research activity, I have witnessed a progressive shift of many scientists to conservative positions on astrocytes’ involvement in synaptic modulation. Many deny that astrocytes can directly impact and modulate synaptic functions. At conferences, I often hear statements supporting a “passive” view of astrocytes’ physiology, such as “I can tell you, there is no endoplasmic reticulum in small processes near synapses”. These statements reveal a general ignorance about how astrocytes appear under the electron microscope. Basic structural details of astrocytes, such as the numbers of synapses in direct contact in a certain volume or the presence/absence of intracellular organelles in a specific domain of these cells are still poorly investigated, and a very limited number of publications is available on this topic. Researchers should be cautious in making strong statements because more research is still needed.

Why did you decide to host a Frontiers Research Topic and what do you hope to achieve from it?

“My research is aimed at developing an effective way to identify the morphological correlates to the phenomena that regulate the physiology of astrocytes. Currently, there is only little evidence in the literature and I hope this special issue will start a new trend, and collect high-quality papers scientists can refer to when describing the influence of astrocytes in neuronal physiology.”

To contribute to our knowledge on astrocytes, submit your manuscript to the Research Topic “The Glia Atlas: an Ultrastructural Insight of Astrocytes at a Microscale Level”!

Laura E Perlini, PhD, Journal Development Specialist Frontiers in Neuroanatomy

neuroscience@frontiersin.org