Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex

Electrical stimulation of the primary visual cortex (V1) is an experimental approach for visual prostheses. We here compared the response to intracortical and epicortical stimulation of the primary visual cortex by using c-Fos immunoreactivity as a marker for neuronal activation.The primary visual cortex of male Sprague Dawley rats was unilaterally stimulated for four hours using bipolar electrodes placed either intracortically in layer IV (n = 26) or epicortically (n = 20). Four different current intensities with a constant pulse width of 200 μs and a constant frequency of 10 Hz were used, for intracortical stimulation with an intensity of 0 μA (sham-stimulation), 10 μA, 20 μA and 40 μA, and for epicortical stimulation 0 μA, 400 μA, 600 μA and 800 μA. Subsequently all animals underwent c-Fos immunostaining and c-Fos expression was assessed in layer I–VI of the primary visual cortex within 200 μm and 400 μm distance to the stimulation site. C-Fos expression was higher after intracortical stimulation compared to epicortical stimulation, even though ten times lower current intensities were applied. Furthermore intracortical stimulation resulted in more focal neuronal activation than epicortical stimulation. C-Fos expression was highest after intracortical stimulation with 20 μA compared to all other intensities. Epicortical stimulation showed a linear increase of c-Fos expression with the highest expression at 800 μA. Sham stimulation showed similar expression of c-Fos in both hemispheres. The contralateral hemisphere was not affected by intracortical or epicortical stimulation of either intensities. In summary, intracortical stimulation resulted in more focal neuronal activation with less current than epicortical stimulation. This model may be used as a simple but reliable model to evaluate electrodes for microstimulation of the primary visual cortex before testing in more complex settings.