Prof. Dr. Volker Busskamp, biotechnologist and research group leader at the UKB Eye Clinic, member of the ImmunoSensation² Cluster of Excellence and the Transdisciplinary Research Area (TRA) ‘Life & Health’ at the University of Bonn, and his team have developed a novel technology that allows human neural networks to be constructed in a targeted and reproducible manner for the first time. The method, called Single-Neuron Network Assembly Platform (SNAP), makes it possible to position nerve cells with single-cell precision and examine their electrical signals. This opens up a completely new approach to researching fundamental processes in the brain – and potentially also diseases such as epilepsy or cardiac arrhythmia.
Targeted neural circuits instead of random networks
Until now, in vitro models of the brain have often been based on randomly formed cell connections, which severely limits their reproducibility. The SNAP method, on the other hand, combines 3D-printed microfluidic channels with state-of-the-art laser and soft lithography technology. The individual cells are positioned in the channels with microscopic precision using a micropipette and a micromanipulator. The axon growth of the nerve cells can also be specifically controlled, resulting in clearly defined and reproducible neural networks. This allows neurons to be positioned exactly and electrical activity to be measured precisely.
‘With SNAP, we can design neural circuits from scratch,’ explains Busskamp. ‘This allows us to study networks with specific properties and to record processes that were previously difficult to access experimentally.’
First direct confirmation of so-called ephaptic coupling
One focus of the study was the investigation of ephaptic coupling – i.e. the interaction between neurons via their own electrical fields, independent of synaptic contacts. Such effects have previously been described mainly in theory, but could hardly be proven experimentally. With SNAP, direct experimental evidence of ephaptic coupling in a controlled human neural circuit has now been obtained for the first time. ‘The decisive factor was being able to control the cells at the single-cell level,’ explains Johannes Striebel, doctoral student and first author of the study. "That sounds trivial, but it is extremely challenging from a technical standpoint. It was only through this precision that we were able to show how electric fields influence signal transmission between neurons." It was found that this form of electrical communication influences the speed and timing of neural signals. Ephaptic coupling probably plays a role not only in the brain but also in the heart muscle and could be involved in diseases such as epilepsy or cardiac arrhythmia.
New opportunities for basic research and disease models
The platform allows the integration of different cell types and the precise observation of individual neurons, including optogenetic stimulation. It can be used both for basic research into information processing in the brain and for modelling disease-specific changes.
In the long term, SNAP could also be used in drug research or in the development of functional disease models. Due to its high sensitivity to synaptic antagonists, the method is particularly suitable for the analysis of neuroactive substances.
