NEURONAL TRACING BY ELECTROCHEMICALLY CONTROLLED IDENTIFICATION OF TARGETS
Relevant for Research Area
Dr. Maria Asplund (Contact PI)
Extracellular electrophysiological recordings in animal models are widely used to investigate brain functionality or pathology. Ideally, the recorded signals can be attributed to underlying neuronal populations, and contribute to a deeper understanding of the mechanisms in neuronal communication or on pathological signal generation. This however presumes that a reconstruction of the electrode position can be made, post mortem, in the histological slices. So far, electrode positions are estimated geometrically, using intrinsic landmarks in the tissue, such as shaft geometry and the surrounding glial scar. Alternatively, burns in the tissue, made by driving faradaic reactions over the electrode, are used as marking method. Since these techniques are not sufficiently precise we have developed a new method to actively stain the microenvironment of recording electrodes using a conducting polymer-based technology in combination with fluorescent lipophilic dyes. A coating based on poly(3,4-ethylene dioxythiophene) (PEDOT) can act as a dye reservoir which can be electrically activated to release the stored molecules. We can thereby provide electrochemically controlled dye delivery directly from the electrode without compromising its recording performance during the preceding period.
In the second funding phase we have worked towards extending our technology to an application, namely to improve our understanding on how electrical stimulation interacts with surrounding tissue. We have designed implantable pH sensors with the purpose of providing continuous monitoring of metabolic reactions surrounding the probe. For this we have studied how the chemical composition of Iridium Oxide (IrOx) can be tuned to accomplish specific pH sensitivity, and how different sputter parameters can be used to realize a differential sensor concept. The aim has been to complement such on-probe sensing technology with PEDOT-based staining of the exact location stimulated. The idea is to combine real time pH sensing at the time point of stimulation with subsequent histological analysis of the surrounding tissue. Such a concept would provide greatly improved opportunities to understand changes in the local microenvironment of a stimulated electrode and how these changes would be correlated to physiological changes over long- and short- term stimulations.
1 S. Heizmann, A. Kilias, U. Egert, P. Ruther and M. Asplund*, "Active control of dye release for neuronal tracing using PEDOT-PSS coated electrodes" in IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2016, DOI:10.1109/TNSRE.2016.2606559. Full paper.
2 Heizmann S, Kilias A, Okujeni S, Boehler C, Ruther P, Egert U, Asplund M (2015) Accurate neuronal tracing of microelectrodes based on PEDOT-dye coatings. In: 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER), pp 386–389. IEEE. Oral presentation and full paper
3 Heizmann S, Holzhammer T, Kilias A, Ruther P, Egert U, Asplund M (2016) "Dye delivery from PEDOT electrodes in vivo - a new way to reconstruct recording sites". Frontiers in Neuroscience: 10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul. Poster and conference paper
4 Heizmann S, Kilias A, Ringwald P, Okujeni S, Böhler C, Ruther P,Egert U, Asplund M (2014) “Precise labeling of microelectrode positions by accurate neuronal tracing based on PEDOT-dye coatings.” FENS Forum of European Neurosciences, Milan, Italy, July 05-09. Poster
5 Heizmann S, Kilias A, Egert U, Ruther P, Asplund M (2015) “In vivo tracing of neurons by advanced dye delivery electrodes” Chicago, IL: Society for Neuroscience (SfN), October 17-21. Poster
6 Heizmann S, Kilias A, Holzhammer T, Ruther P, Egert U, Asplund M (2016) “Precise neurotracer delivery on chip”. European Material Research Society (EMRS), Lille, France, May 02-06. Oral presentation
7 F. Barz, P. Ruther and M. Asplund, “Influence of the Oxygen Flow Rate on the pH Response of Reactively Sputter Deposited Iridium Oxide Films”, 40th Annual Conference on Engineering in Biology Society IEEE/EMBC, Honolulu, July, 2018. 1- page paper contribution / Poster.