Rapid neurostimulation at the micron scale with an optically controlled thermal-capture technique

Abstract

Precise control of cellular temperature at the microscale is crucial for developing novel neurostimulation techniques. Here, the effect of local heat on the electrophysiological properties of primary neuronal cultures and HEK293 cells at the subcellular level using a cutting-edge micrometer-scale thermal probe, the diamond heater-thermometer (DHT), is studied. A new mode of local heat action on a living cell, thermal-capture mode (TCM), is discovered using the DHT probe. In TCM, the application of a 50 °C temperature step induces a great increase in cellular response, allowing the cell to be thermally captured and depolarized by up to 20 mV. This thermal effect is attributed to local phase changes in the phospholipid membrane, enabling precise and reproducible modulation of cell activity. The TCM is shown to open up new opportunities for thermal cell stimulation. DHT reliably triggers action potentials (APs) in neurons at rates up to 30 Hz, demonstrating the ability to control cell excitability with millisecond and sub-millisecond resolution. AP shape is modulated by local heat as well. The ability to precisely control the AP shape and rate via thermal-capture mode opens new avenues for non-invasive, localized neurostimulation techniques, particularly in controlling neuron excitability.