To mark World Brain Day, celebrated on 22 July, the Biofisika Institute (CSIC, EHU and a BERC — Basque Excellence Research Centre) is highlighting the progress made by one of its research teams in understanding the brain’s microscopic architecture. The group led by Jan Tönnesen has succeeded in directly visualising the extracellular space (the tiny region separating neurons) a territory that until now had been almost inaccessible to observation in living tissue.
This space, which plays a key role in neuronal communication, is where the neurotransmitters that enable signals to be exchanged between cells are diffused. “Traditionally, research has focused on the transmitting and receiving neurons. Our approach is to understand how the environment between neurons itself modulates the signal,” explains Tönnesen, the group’s principal investigator.
This breakthrough has been made possible by a new generation of fluorescence microscopy that enables structures to be observed at the nanometre scale. The technique, known as super-resolution shadow imaging (SUSHI), uses negative contrast to reveal the geometry of the extracellular space with great precision. This approach opens the door to studying how its organisation influences processes such as cognition, brain ageing and the development of disease.
“If we are successful, we may eventually be able to target therapies for neurodegenerative diseases such as Parkinson’s more effectively, or to understand how deterioration associated with age and biological factors occurs,” says Alejandro Fierro, a predoctoral researcher in the group. His day-to-day work includes maintaining living cell cultures using specialised culture media, which allow tissues to be observed under controlled conditions for several hours.
The laboratory combines these cultures with solutions designed to reproduce the brain’s energy environment, which is highly dependent on glucose. This experimental control facilitates the study of the structure and functioning of brain tissue under conditions similar to physiological ones.
The ability to analyse the brain’s structural complexity at this level of detail represents a significant leap forward. “We can now observe aspects that were previously invisible and gain a better understanding of how neurons connect and how brain activity is generated,” Fierro adds.
According to the World Health Organization, neurological diseases are among the leading causes of disability worldwide, affecting hundreds of millions of people. Parkinson’s disease alone affects more than 8.5 million people globally (WHO, 2022). These figures underline the importance of research that helps improve our understanding and treatment of these conditions.
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