The Space Between Neurons: A Territory Yet to Be Explored in Understanding Brain Ageing and Diseases such as Parkinson’s

22 July marks World Brain Day

“Traditionally, research has focused on the transmitting neuron and the receiving neuron. Our approach is to understand how the environment between neurons itself modulates that signal,” says researcher Jan Tönnesen.

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To mark World Brain Day, celebrated on 22 July, the Biofisika Institute (CSIC, the University of the Basque Country UPV/EHU and the BERC Centre of Excellence) located at the Basque Country Technology Park’s Leioa Campus, is highlighting the advances 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 that separates neurons and a territory that has until now been virtually inaccessible to live observation.

This space, which is crucial to neuronal communication, is where neurotransmitters diffuse, enabling the exchange of signals between cells. “Traditionally, research has focused on the transmitting neuron and the receiving neuron. Our approach is to understand how the environment between neurons itself modulates that signal,” explains Tönnesen, Principal Investigator.

The breakthrough has been made possible by a new generation of fluorescence microscopy capable of observing structures at the nanometre scale. The technique, known as super-resolution shadow imaging (SUSI), provides negative contrast imaging that reveals the geometry of the extracellular space with remarkable precision. This approach opens up new possibilities for studying how its organisation influences processes such as cognition, brain ageing and the development of neurological disorders.

“If we are successful, in the future we will be able to better target therapies for neurodegenerative diseases such as Parkinson’s, and gain a deeper understanding of how deterioration associated with ageing and biological factors occurs,” says Alejandro Fierro, a predoctoral researcher in the group. His daily work includes maintaining living cell cultures using specialised media, allowing tissues to be observed under controlled conditions for extended periods.

The laboratory combines these cultures with solutions designed to replicate the brain’s energy environment, which is highly dependent on glucose. This experimental control facilitates the study of brain tissue structure and function under conditions that closely resemble physiological reality.

The possibility of analysing the brain’s structural complexity at this level of detail represents a significant step 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,” adds Fierro.

According to the World Health Organization, neurological disorders 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 advances our understanding and treatment of such conditions.