Intracortical microstimulation differentially activates cortical layers based on stimulation depth

•Intracortical microstimulation was combined with extracellular recordings in vivo.•Responses to low current (<15 μA) electrical stimulation were layer specific.•Most natural responses were achieved when stimulating layer IV.

BackgroundIntracortical microstimulation is one of the most common techniques to causally interfere with neuronal processing, but neuronal recordings spanning the whole cortical depth during stimulation are exceptionally rare.Objective/HypothesisHere we combined layer-specific intracortical microstimulation with extracellular recordings on the same shank of a linear multi-electrode array to study the effects of electrical stimulation in different cortical depths on intracortical processing in the auditory cortex in vivo.MethodsPopulation responses (local field potentials and multi-unit activity) were recorded from the auditory cortex of 8 guinea pigs under ketamine/xylazine anesthesia while single current pulses (charge-balanced, biphasic, square-wave, 0.1-45 μA, 200 μs/phase) were delivered in different cortical depths.ResultsThe cortical responses differed with a change in the stimulation parameters, with significant factors being the stimulating current (p < 0.0001), stimulation depth (p = 0.03) and the recording depth (p = 0.002) considering the local field potential amplitude. A cross-correlation analysis between responses evoked by intracortical microstimulation and physiological auditory stimuli revealed the closest match when stimulating the middle granular layer (p < 0.05).ConclusionIntracortical response profiles to low-current intracortical microstimulation were layer specific. The most natural cortical response was achieved by stimulation in the thalamo-recipient layer. These findings contribute to a basis for designing cortical neuroprosthetics.