Identifying and Manipulating Key Neurons
In our research, we focus on the fascinating world of neurons, the cells that communicate and shape how we think, learn, and remember. Our goal is understanding how to selectively “speak” to these cells through cutting-edge techniques including optogenetic, mechanical, and electrical stimulation.
Why manipulate neurons? Imagine a network of friends sharing ideas—if one person starts a conversation, it can ripple through the group. Similarly, some neurons play key roles in how brain networks function, and by activating these “influential” neurons, we can study how they affect the entire network's behavior. This research could help us discover new ways to influence brain activity in targeted, efficient ways, opening doors to potential therapies for neurological conditions. Furthermore, how we stimulate a network will engage a different number of neurons for a different duration – just as a laugh or a sneeze in the conversational group will trigger different responses at different distances. We need to quantify these responses in order for stimulation programs to effectively communicate with neuronal networks.
How do we do it? We have observed that poking a single neuron can trigger mechanical responses that propagate through the network for hundreds of micrometers and last for up to 10 minutes. With the aim of higher spatial specificity, we use a special protein called channelrhodopsin to sensitize neurons to light. By targeting a specific neuron with a laser, we can trigger it to send signals, allowing us to observe how this activity influences surrounding neurons and maps connections within the network. This lays a framework to potentially guide network activity, with a focus on understanding memory, information processing, and network resilience.
Precise activation allows us to test how individual neurons contribute to network dynamics, helping to unravel the intricate conversations within a neuronal network. Electrical stimulation using devices designed in Jülich, or their commercial counterparts completes the toolbox we are characterizing for network stimulation.
Papers:
Cepkenovic, B., Friedland, F., Noetzel, E., Maybeck, V., & Offenhäusser, A. (2023). Single-neuron mechanical perturbation evokes calcium plateaus that excite and modulate the network. Scientific Reports, 13(1), 20669. https://doi.org/10.1038/s41598-023-47090-z https://www.nature.com/articles/s41598-023-47090-z
Maybeck, V., Schnitker, J., Li, W., Heuschkel, M., & Offenhausser, A. (2016). An evaluation of extracellular MEA versus optogenetic stimulation of cortical neurons. Biomedical Physics and Engineering Express, 2(5). https://doi.org/10.1088/2057-1976/2/5/055017 https://iopscience.iop.org/article/10.1088/2057-1976/2/5/055017