Neurons & Axons
The brain’s unique abilities, such as perceptions, memory, and learning are believed to emerge from the interactions of networks of external pageneurons. To investigate such interactions and neuronal information processing in general, we grow primary or stem-cell-derived neurons in vitro over high-density CMOS microelectrode arrays developed in house. A number of additional tools supplement our research including: gene transfection techniques for live-cell imaging of cell compartments; microfluidic devices to amplify neuronal signals and control neuronal growth on the arrays; and more traditional tools, such as immunohistochemistry and intracellular patch electrophysiology.
Owing to a flexible design, each of the thousands of electrodes of an array can be used to either record or stimulate neuronal activity, providing bidirectional access to any neuron in the culture. A special feature is the array’s ability to detect small signals from action potentials traveling along an external pageaxon, opening a new frontier in axon electrophysiology. Axonal action potentials displayed a surprisingly large variability, and we are investigating their possible involvement in neuronal information processing. Furthermore, the high spatio-temporal resolution data provided by the arrays allow us to characterize the electrical-neuronal interface. Such knowledge can help instruct the design of future external pagebrain-machine interfaces.
Somatic and propagating action potentials can be evoked by electrical stimulation. Stimuli are repeatedly applied to a single electrode (white cross in the movies below) while scanning recording configurations throughout the whole array of electrodes (1.8 × 2.0 mm2) or a selected subset. The median voltages per electrode in response to approximately 60 stimuli per configuration are color-coded and show action potentials evoked in a subset of somas and/or axons. The color scale was clipped in order to better observe propagating action potentials (yellowish).
Movie Action Potential Tracing: Somatic (blue) and propagating (yellow) action potentials upon electrical stimulation. Stimuli were repeatedly applied to a single electrode (white cross). Each frame includes 95 electrode configurations.
Movie Axonal Propagation: Stimuli were applied via a single electrode (white cross) to a stained neuron. Evoked action potentials propagate from the stimulation site backwards along the axon toward the soma.
Collaborations
Friedrich-Miescher Institute, Basel, Switzerland; Riken, Kobe, Japan; University of Tokyo, Japan; University of Freiburg, Germany.
Recent publications
X. Yuan, M. Schröter, M. Engelene J. Obien, M. Fiscella, W. Gong, T. Kikuchi, A. Odawara, S. Noji, I. Suzuki, J. Takahashi, A. Hierlemann, U. Frey, "Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level", Nature Communications 2020, 11, 4854 (DOI: 10.1038/s41467-020-18620-4). external pageOnline
V. Emmenegger, M. Engelene Obien, F. Franke, A. Hierlemann, "Technologies to study action potential propagation with a focus on HD-MEAs", Frontiers in Cellular Neuroscience 2019, 13, Article 159 (DOI: 10.3389/fncel.2019.00159). external pageOnline
S. Ronchi, M. Fiscella, C. Marchetti, V. Viswam, J. Müller, U. Frey, A. Hierlemann, "Single-cell electrical stimulation using CMOS-based high-density microelectrode arrays", Frontiers in Neuroscience 2019, 13, Article 208 (DOI: 10.3389/fnins.2019.00208). external pageOnline
D. Bakkum, M. Engelene J. Obien, M. Radivojevic, D. Jäckel, U. Frey, H. Takahashi, A. Hierlemann, "The axon initial segment is the dominant contributor to the neuron's extracellular electrical potential landscape", Advanced Biosystems 2018, 1800308 (DOI: 10.1002/adbi.201800308). external pageOnline
M. Radivojevic, D. Jäckel, M. Altermatt, J. Müller, V. Viswam, A. Hierlemann, D. Bakkum, "Electrical identification and selective microstimulation of neuronal compartments based on features of extracellular action potentials", Scientific Reports 2016, 6, 31332 (DOI:10.1038/srep31332). external pageOnline