Stimulation with ECoG electrodes modulates cortical activity and sensory processing in the awake mouse brain

Electrical stimulation has been widely used to probe neural network properties and treat dysfunction. Electrocorticography (ECoG) electrodes, long used for activity monitoring, can also stimulate the brain in a minimally invasive and chronic manner. However, how cortical surface electrical stimulation impacts cortical network activity remains poorly understood. Using in vivo calcium imaging in the awake mouse brain with chronically implanted ECoG electrodes, we measured how electrical stimulation modulates the activity of visual cortical neurons, including during concurrent visual stimulation. We found that cortical surface electrical stimulation initially activates L2/3 neurons followed by prolonged inhibition lasting seconds after stimulation. Electrical stimulation suppresses the activity of neurons at their preferred grating orientation but enhances their responses to non-preferred visual stimuli, thereby reducing sensory feature selectivity. By measuring how electrical stimulation modulates the activity of inhibitory neuron subtypes including PV, SST, and NDNF interneurons, we propose a circuit model in which L1 NDNF interneurons are strongly activated by cortical electrical stimulation and, in turn, inhibit L2/3 excitatory neurons and PV interneurons through volume transmission of GABA.