Light-Evoked Modulation of Neuronal Activity with Conjugated Polymers
Organic bioelectronics aims at the intimate integration between organic materials and biological tissues in order to obtain a targeted functional outcome. In the last decades, conductive polymers have been successfully employed to interface excitable cells through biocompatible probes and devices. We previously reported the possibility to culture primary neurons on photosensitive conjugated polymers, such as poly(3-hexylthiophene) (P3HT), without altering either the polymer or the neuronal properties. These neurons displayed a depolarizing response to a brief (< 50 ms) green light stimulus and a consequent control over the action potential firing rate. The same interface was also shown to elicit activation of retinal circuitry and ganglion cell firing in explanted degenerate retinas upon light stimulation. However, while neuronal excitation has been extensively proved via planar or protruding electrodes, carbon nanotubes, and conjugated polymers, the hyperpolarization of neurons and silencing of their firing activity has been achieved with optogenetics, but rarely documented for functionalized planar devices and structures. We show here a method to induce both depolarization and hyperpolarization of cells interfaced with conjugated polymers upon prolonged (500 ms) light stimulation. Patch-clamp experiments showed that HEK293 cells grown on P3HT displayed a biphasic response composed of an initial depolarization followed by a sustained hyperpolarization during light illumination. We also documented that the amplitude of the light-induced hyperpolarization was reduced in the absence of intracellular potassium, but was insensitive to changes in the intracellular chloride concentration. A prolonged illumination was equally able to hyperpolarize primary neurons cultured over P3HT and significantly reduced both spontaneous and electrically elicited action potential frequency. We further assessed the translatability of our findings to tissue stimulation by describing the modulation of ganglion cell firing in explanted blind retinas from Royal College of Surgeons rats, a model of Retinitis pigmentosa. By coupling conjugated polymers with multi-electrode arrays and conventional metal electrodes, single-unit activity of ganglion cells was inhibited by prolonged illumination. We similarly investigated the phenomenon in acute hippocampal brain slices placed onto a conjugated polymer thin film. These results indicate that conjugated polymers can be used to non-invasively excite and inhibit the electrical activity of cells cultured on its surface. Furthermore, the translation of our findings from in vitro cultures to different central nervous system tissues, suggests a potential application of these organic devices as a tool for modulation of neuronal activity in vivo.
Record created on 2015-08-22, modified on 2017-01-23