Christin Schülke

• Pabst, Oliver; Schülke, Christin; Balasingham, Ilangko; Krauss, Stefan Johannes Karl; Glover, Joel Clinton & Martinsen, Ørjan Grøttem (2025). Recording and modeling of pinched hysteresis loops, the fingerprint of a memristor, in neurons. Scientific Reports. 15. doi: 10.1038/s41598-025-21035-0. Full text in Research Archive Show summary

  A variant of the Hodgkin-Huxley model has been proposed in which time-varying Na+ and K+ ion conductances are replaced by memristors, based on the proposal that ion channels are memristors. This hypothesis predicts that current-voltage plots of neurons subjected to sinusoidal stimulation should exhibit a pinched hysteresis loop, the fingerprint of a memristor. We tested this using whole-cell patch clamp recordings from human neurons derived from neural progenitor cells and observed pinched hysteresis loops in 16% of all recorded neurons. Recordings with current clamp and voltage clamp with a holding potential of 0 mV yielded a higher success rate than voltage clamp recordings with a holding potential of around − 60 mV. In addition, more neurons exhibited pinched hysteresis loops when the applied voltage or current amplitude was high, and the frequency was low. The recording of pinched hysteresis loops in neurons gives evidence that these contain memristors and this is the first time to be shown experimentally. This is not just an indication that the memristor-based Hodgkin-Huxley model is valid; it also demonstrates that models of neurons based on memristors actually resemble nature. We then subjected simulated neurons expressing Hodgkin-Huxley voltage-gated Na+ and K+ channels to sinusoidal membrane potential oscillations and found that the presence of pinched hysteresis loops depended strongly on the density of voltage-gated K+ channels and on the membrane capacitance but not on the presence of voltage-gated Na+ channels. Because Na+ channels are expected to be largely inactivated in neurons at a holding potential of 0 mV, these findings together suggest that it is the presence of voltage-gated K+ channels that is critical for the observed memristive behavior.

• Cunha, André; Schülke, Christin; Mesri, Alireza; Ruud, Simen Kristoffer; Aizenshtadt, Aleksandra & Ferrari, Giorgio [Show all 16 contributors for this article] (2024). Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant. Sensors. 24(2). doi: 10.3390/s24020575. Full text in Research Archive Show summary

  Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.

• Hou, Jie; Abie, Sisay Mebre; Strand-Amundsen, Runar James; Galperin, Yuri; Bergli, Joakim & Schuelke, Christin [Show all 8 contributors for this article] (2021). Temperature dependence of the microwave dielectric properties of γ -aminobutyric acid. Scientific Reports. 11(1). doi: 10.1038/s41598-021-97178-7. Full text in Research Archive Show summary

  The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces the neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Earlier studies suggest that recognition is determined by the geometries of the molecule and its receptor. We employed dielectric relaxation spectroscopy (DRS) to study the conformation and dielectric properties of the GABA molecule under physiologically relevant laboratory conditions. The dielectric properties of GABA investigated have given us new insights about the GABA molecule, such as how they interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperature leads to lower viscosity, thus lower relaxation time. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. A resonance behavior was observed with high GABA concentrations at physiological temperature, where there might be a phase transition at a certain temperature for a given GABA concentration that leads to a sudden change of the dielectric properties.

• Cunha, Andrè Bastos da; Schuelke, Christin; Heiskanen, Arto; Asif, Afia; Hassan, Yasmin M. & Keller, Stephan S. [Show all 10 contributors for this article] (2020). Bioimpedance Measurements on Human Neural Stem Cells as a Benchmark for the Development of Smart Mobile Biomedical Applications. International Federation for Medical and Biological Engineering Proceedings. ISSN 1680-0737. 72, p. 38–47. doi: 10.1007/978-981-13-3498-6_6. Full text in Research Archive Show summary

  Over the past 30 years, stem cell technologies matured from an attractive option to investigate neurodegenerative diseases to a possible paradigm shift in their treatment through the development of cell-based regenerative medicine (CRM). Implantable cell replacement therapies promise to completely restore function of neural structures possibly changing how we currently perceive the onset of these conditions. One of the major clinical hurdles facing the routine implementation of stem cell therapy is the limited and inconsistent benefit observed thus far. While unclear, numerous pre-clinical and a handful of clinical cell fate imaging studies point to poor cell retention and survival. Coupling the need to better understand these mechanisms while providing scalable approaches to monitor these treatments in both pre-clinical and clinical scenarios, we show a proof of concept bioimpedance electronic platform for the Agile development of smart and mobile biomedical applications like neural implants or highly portable monitoring devices.

• Cunha, Andrè Bastos da; Hou, Jie & Schuelke, Christin (2019). Machine learning for stem cell differentiation and proliferation classification on electrical impedance spectroscopy. Journal of Electrical Bioimpedance. 10(1), p. 124–132. doi: 10.2478/joeb-2019-0018. Full text in Research Archive Show summary

  Electrical impedance spectroscopy (EIS) measurements on cells is a proven method to assess stem cell proliferation and differentiation. Cell regenerative medicine (CRM) is an emerging field where the need to develop and deploy stem cell assessment techniques is paramount as experimental treatments reach pre-clinical and clinical stages. However, EIS measurements on cells is a method requiring extensive post-processing and analysis. As a contribution to address this concern, we developed three machine learning models for three different stem cell lines able to classify the measured data as proliferation or differentiation laying the stone for future studies on using machine learning to profile EIS measurements on stem cells spectra.

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• Schuelke, Christin; Cunha, Andrè Bastos da; Heiskanen, Arto; Asif, Afia; Keller, Stephan S. & Martínez-Serrano, Alberto [Show all 8 contributors for this article] (2020). Neural Stem Cell Characterization and Detection of Neurotransmitter release using Bioimpedance and Electrochemistry. Full text in Research Archive Show summary

  The goal of the Training4CRM project is to develop a device for personalized medicine to treat neurodegenerative disorders (Parkinson´s Disease, Huntington´s Disease, and Epilepsy). This future device includes a bioimplant consisting of a 3D scaffold, electronics, a light source and optogenetically modified neuronal cells that will be operated into the patient’s brain to release disease-specific neurotransmitters. The aim of this work is the non-invasive observation of cell proliferation and neuronal differentiation, as well as detection of neurotransmitter release. Electrical Impedance Spectroscopy (EIS) and amperometry provide excellent tools for investigation of various cellular phenomena. EIS can be used to monitor different cellular changes like proliferation, apoptosis, migration, changes in morphology and also (neuronal) differentiation. Compared to most molecular biological methods, bioimpedance measurements are non-invasive and allow for repeated analysis of the same cell population. Human neural stem cells were cultured as monolayer on 2D carbon electrode chips. Bioimpedance measurements were performed every second day to follow the proliferation of hNSCs. Cells impede the flow of current between electrodes. Therefore, an increasing number of cells results in an increased impedance. Amperometry was used to detect the release of neurotransmitters (especially dopamine) after triggered depolarization by stimulation of neurons with a high K+ buffer. Release of oxidizable molecules leads to increased current visible as oxidation peak. This work demonstrates the principle of bioimpedance and electrochemical detection of neurotransmitter release. With EIS, proliferation can be monitored noninvasively over time. With amperometry, detection of repeated depolarization is possible and cells remain active over several days.

• Salado-Manzano, Cristina; Schuelke, Christin; Gonzalez-Ramos, Ana; Waloschková, Eliška; Baumlin, Camille & Vasudevan, Shashank [Show all 14 contributors for this article] (2019). European Union Horizon2020: Training4CRM ITN. Cell-based therapies for neurodegenerative diseases. Full text in Research Archive
• Schuelke, Christin; Cunha, Andrè Bastos da; Heiskanen, Arto; Asif, Afia; Keller, Stephan S. & Kalvøy, Håvard [Show all 9 contributors for this article] (2019). Bioimpedance and Electrochemistry for Neural Stem Cell Characterization and Detection of Dopamine Release. IEEE Engineering in Medicine and Biology Society. Conference Proceedings. ISSN 1557-170X. Full text in Research Archive Show summary

  Biophysical measurement methods like electrical impedance spectroscopy and amperometry provide an excellent tool for investigation of various cellular phenomena. In this work, bioimpedance measurements have been performed to assess the proliferation of neural stem cells or PC12 cells. Subsequently, amperometry was used to detect neurotransmitter release from PC12 cells or neurons differentiated from neural stem cells.

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