Preclinical model of transcorneal alternating current stimulation in freely moving rats

Abstract

Purpose: Transcorneal alternating current stimulation (tACS) has become a promising tool to modulate brain functions and treat visual diseases. To understand the mechanisms of action a suitable animal model is required. However, because existing animal models employ narcosis, which interferes with brain oscillations and stimulation effects, we developed an experimental setup where current stimulation via the eye and flicker light stimulation can be applied while simultaneously recording local field potentials in awake rats. Method: tACS was applied in freely-moving rats (N= 24) which had wires implanted under their upper eye lids. Field potential recordings were made in visual cortex and superior colliculus. To measure visual evoked responses, rats were exposed to flicker-light using LEDs positioned in headset spectacles. Results: Corneal electrodes and recording assemblies were reliably operating and well tolerated for at least 4 weeks. Transcorneal stimulation without narcosis did not induce any adverse reactions. Stable head stages allowed repetitive and long-lasting recordings of visual and electrically evoked potentials in freely moving animals. Shape and latencies of electrically evoked responses measured in the superior colliculus and visual cortex indicate that specific physiological responses could be recorded after tACS. Conclusions: Our setup allows the stimulation of the visual system in unanaesthetised rodents with flicker light and transcorneally applied current travelling along the physiological signalling pathway. This methodology provides the experimental basis for further studies of recovery and restoration of vision.